Online Mendelian Inheritance in Man (OMIM) (2023)

  1. Adler, M. J., Coronel, C., Shelton, E., Seegmiller, J. E., Dewji, N. N. Increased gene expression of Alzheimer disease beta-amyloid precursor protein in senescent cultured fibroblasts. Proc. Nat. Acad. Sci. 88: 16-20, 1991. [PubMed: 1702541] [Full Text: https://doi.org/10.1073/pnas.88.1.16]

  2. Ahn, H. J., Glickman, J. F., Poon, K. L., Zamolodchikov, D., Jno-Charles, O. C., Norris, E. H., Strickland, S. A novel A-beta-fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice. J. Exp. Med. 211: 1049-1062, 2014. [PubMed: 24821909] [Full Text: https://doi.org/10.1084/jem.20131751]

  3. Ancolio, K., Dumanchin, C., Barelli, H., Warter, J. M., Brice, A., Campion, D., Frebourg, T., Checler, F. Unusual phenotypic alteration of beta amyloid precursor protein (beta-APP) maturation by a new val715-to-met beta-APP-770 mutation responsible for probable early-onset Alzheimer's disease. Proc. Nat. Acad. Sci. 96: 4119-4124, 1999. [PubMed: 10097173] [Full Text: https://doi.org/10.1073/pnas.96.7.4119]

  4. Baek, S. H., Ohgi, K. A., Rose, D. W., Koo, E. H., Glass, C. K., Rosenfeld, M. G. Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappa-B and beta-amyloid precursor protein. Cell 110: 55-67, 2002. [PubMed: 12150997] [Full Text: https://doi.org/10.1016/s0092-8674(02)00809-7]

  5. Bakker, E., van Broeckhoven, C., Haan, J., Voorhoeve, E., van Hul, W., Levy, E., Lieberburg, I., Carman, M. D., van Ommen, G. J. B., Frangione, B., Roos, R. A. C. DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type). Am. J. Hum. Genet. 49: 518-521, 1991. [PubMed: 1679289]

  6. Balbin, M., Abrahamson, M., Gustafson, L., Nilsson, K., Brun, A., Grubb, A. A novel mutation in the beta-protein coding region of the amyloid beta-protein precursor (APP) gene. Hum. Genet. 89: 580-582, 1992. [PubMed: 1634237] [Full Text: https://doi.org/10.1007/BF00219191]

  7. Bales, K. R., Verina, T., Cummins, D. J., Du, Y., Dodel, R. C., Saura, J., Fishman, C. E., DeLong, C. A., Piccardo, P., Petegnief, V., Ghetti, B., Paul, S. M. Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. Proc. Nat. Acad. Sci. 96: 15233-15238, 1999. [PubMed: 10611368] [Full Text: https://doi.org/10.1073/pnas.96.26.15233]

  8. Barrett, P. J., Song, Y., Van Horn, W. D., Hustedt, E. J., Schafer, J. M., Hadziselimovic, A., Beel, A. J., Sanders, C. R. The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science 336: 1168-1171, 2012. [PubMed: 22654059] [Full Text: https://doi.org/10.1126/science.1219988]

  9. Basun, H., Bogdanovic, N., Ingelsson, M., Almkvist, O., Naslund, J., Axelman, K., Bird, T. D., Nochlin, D., Schellenberg, G. D., Wahlund, L.-O., Lannfelt, L. Clinical and neuropathological features of the Arctic APP gene mutation causing early-onset Alzheimer disease. Arch. Neurol. 65: 499-505, 2008. [PubMed: 18413473] [Full Text: https://doi.org/10.1001/archneur.65.4.499]

  10. Blanquet, V., Goldgaber, D., Turleau, C., Creau-Goldberg, N., Delabar, J., Sinet, P. M., Roudier, M., de Grouchy, J. In situ hybridization of the beta amyloid protein (APP) cDNA to the vicinity of the interface of 21q21 and q22 in normal and Alzheimer's disease individuals. (Abstract) Cytogenet. Cell Genet. 46: 582 only, 1987.

  11. Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., Holtzman, D. M. Amyloid-beta dynamics correlate with neurological status in the injured human brain. Science 321: 1221-1224, 2008. [PubMed: 18755980] [Full Text: https://doi.org/10.1126/science.1161591]

  12. Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., Stefani, M. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416: 507-511, 2002. [PubMed: 11932737] [Full Text: https://doi.org/10.1038/416507a]

  13. Bugiani, O., Giaccone, G., Rossi, G., Mangieri, M., Capobianco, R., Morbin, M., Mazzoleni, G., Cupidi, C., Marcon, G., Giovagnoli, A., Bizzi, A., Di Fede, G., Puoti, G., Carella, F., Salmaggi, A., Romorini, A., Patruno, G. M., Magoni, M., Padovani, A., Tagliavini, F. Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP. Arch. Neurol. 67: 987-995, 2010. [PubMed: 20697050] [Full Text: https://doi.org/10.1001/archneurol.2010.178]

  14. Burns, M. P., Zhang, L., Rebeck, G. W., Querfurth, H. W., Moussa, C. E.-H. Parkin promotes intracellular A-beta-1-42 clearance. Hum. Molec. Genet. 18: 3206-3216, 2009. [PubMed: 19483198] [Full Text: https://doi.org/10.1093/hmg/ddp258]

  15. Cai, D., Zhong, M., Wang, R., Netzer, W. J., Shields, D., Zheng, H., Sisodia, S. S., Foster, D. A., Gorelick, F. S., Xu, H., Greengard, P. Phospholipase D1 corrects impaired beta-APP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons. Proc. Nat. Acad. Sci. 103: 1936-1940, 2006. [PubMed: 16449385] [Full Text: https://doi.org/10.1073/pnas.0510710103]

  16. Calhoun, M. E., Wiederhold, K.-H., Abramowski, D., Phinney, A. L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B., Jucker, M. Neuron loss in APP transgenic mice. Nature 395: 755-756, 1998. [PubMed: 9796810] [Full Text: https://doi.org/10.1038/27351]

  17. Campion, D., Dumanchin, C., Hannequin, D., Dubois, B., Belliard, S., Puel, M., Thomas-Anterion, C., Michon, A., Martin, C., Charbonnier, F., Raux, G., Camuzat, A., Penet, C., Mesnage, V., Martinez, M., Clerget-Darpoux, F., Brice, A., Frebourg, T. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am. J. Hum. Genet. 65: 664-670, 1999. [PubMed: 10441572] [Full Text: https://doi.org/10.1086/302553]

  18. Cao, X., Sudhof, T. C. A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293: 115-120, 2001. Note: Erratum: Science 293: 1437 only, 2001. [PubMed: 11441186] [Full Text: https://doi.org/10.1126/science.1058783]

  19. Carter, D. A., Desmarais, E., Bellis, M., Campion, D., Clerget-Darpoux, F., Brice, A., Agid, Y., Jaillard-Serradt, A., Mallet, J. More missense in amyloid gene. (Letter) Nature Genet. 2: 255-256, 1992. [PubMed: 1303275] [Full Text: https://doi.org/10.1038/ng1292-255]

  20. Carter, D., Campion, D., d'Amato, T., Jay, M., Brice, A., Bellis, M., Mallet, J., Agid, Y. No mutation in codon 713 of the amyloid precursor gene in schizophrenic patients. Hum. Molec. Genet. 2: 321, 1993. [PubMed: 8499923] [Full Text: https://doi.org/10.1093/hmg/2.3.321]

  21. Chartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., Mullan, M. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 353: 844-846, 1991. [PubMed: 1944558] [Full Text: https://doi.org/10.1038/353844a0]

  22. Chen, A. C., Selkoe, D. J. Response to: Pardossi-Piquard et al., 'Presenilin-dependent transcriptional control of the A-beta-degrading enzyme neprilysin by intracellular domains of beta-APP and APLP'. Neuron 46, 541-554. Neuron 53: 479-483, 2007. [PubMed: 17296549] [Full Text: https://doi.org/10.1016/j.neuron.2007.01.023]

  23. Cheng, I. H., Palop, J. J., Esposito, L. A., Bien-Ly, N., Yan, F., Mucke, L. Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation. Nature Med. 10: 1190-1192, 2004. [PubMed: 15502844] [Full Text: https://doi.org/10.1038/nm1123]

  24. Cheng, S. V., Nadeau, J. H., Tanzi, R. E., Watkins, P. C., Sacchi, N., Neve, R. L., Gusella, J. F. Synteny in man and mouse of DNA markers from the chromosomal region linked to familial Alzheimer's disease and Down syndrome. (Abstract) Am. J. Hum. Genet. 41: A161 only, 1987.

  25. Cherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., McLean, C. A., Barnham, K. J., Volitakis, I., Fraser, F. W., Kim, Y.-S., Huang, X., Goldstein, L. E., Moir, R. D., Lim, J. T., Beyreuther, K., Zheng, H., Tanzi, R. E., Masters, C. L., Bush, A. I. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30: 665-676, 2001. [PubMed: 11430801] [Full Text: https://doi.org/10.1016/s0896-6273(01)00317-8]

  26. Choi, D.-S., Wang, D., Yu, G.-Q., Zhu, G., Kharazia, V. N., Paredes, J. P., Chang, W. S., Deitchman, J. K., Mucke, L., Messing, R. O. PKC-epsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice. Proc. Nat. Acad. Sci. 103: 8215-8220, 2006. [PubMed: 16698938] [Full Text: https://doi.org/10.1073/pnas.0509725103]

  27. Chu, J., Pratico, D. 5-lipoxygenase as an endogenous modulator of amyloid-beta formation in vivo. Ann. Neurol. 69: 34-46, 2011. [PubMed: 21280074] [Full Text: https://doi.org/10.1002/ana.22234]

  28. Cisse, M., Halabisky, B., Harris, J., Devidze, N., Dubal, D. B., Sun, B., Orr, A., Lotz, G., Kim, D. H., Hamto, P., Ho, K., Yu, G.-Q., Mucke, L. Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 469: 47-52, 2011. [PubMed: 21113149] [Full Text: https://doi.org/10.1038/nature09635]

  29. Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., Selkoe, D. J. Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature 360: 672-674, 1992. [PubMed: 1465129] [Full Text: https://doi.org/10.1038/360672a0]

  30. Citron, M., Vigo-Pelfrey, C., Teplow, D. B., Miller, C., Schenk, D., Johnston, J., Winblad, B., Venizelos, N., Lannfelt, L., Selkoe, D. J. Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc. Nat. Acad. Sci. 91: 11993-11997, 1994. [PubMed: 7991571] [Full Text: https://doi.org/10.1073/pnas.91.25.11993]

  31. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A., Kholodenko, D., Motter, R., Sherrington, R., Perry, B., Yao, H., Strome, R., Lieberburg, I., Rommens, J., Kim. S., Schenk, D., Fraser, P., St. George Hyslop, P., Selkoe, D. J. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nature Med. 3: 67-72, 1997. [PubMed: 8986743] [Full Text: https://doi.org/10.1038/nm0197-67]

  32. Colton, C. A., Vitek, M. P., Wink, D. A., Xu, Q., Cantillana, V., Previti, M. L., Van Nostrand, W. E., Weinberg, J. B., Dawson, H. NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease. Proc. Nat. Acad. Sci. 103: 12867-12872, 2006. Note: Erratum: Proc. Nat. Acad. Sci 103: 15273 only, 2006. [PubMed: 16908860] [Full Text: https://doi.org/10.1073/pnas.0601075103]

  33. Coon, H., Hoff, M., Holik, J., Delisi, L. E., Crowe, T., Freedman, R., Shields, G., Boccio, A. M., Lerman, M., Gershon, E. S., Gejman, P. V., Leppert, M., Byerley, W. C to T nucleotide substitution in codon 713 of amyloid precursor protein gene not found in 86 unrelated schizophrenics from multiplex families. Am. J. Med. Genet. 48: 36-39, 1993. [PubMed: 8102836] [Full Text: https://doi.org/10.1002/ajmg.1320480109]

  34. Cras, P., van Harskamp, F., Hendriks, L., Ceuterick, C., van Duijn, C. M., Stefanko, S. Z., Hofman, A., Kros, J. M., Van Broeckhoven, C., Martin, J. J. Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692ala-gly mutation. Acta Neuropath. 96: 253-260, 1998. [PubMed: 9754958] [Full Text: https://doi.org/10.1007/s004010050892]

  35. De Jonghe, C., Esselens, C., Kumar-Singh, S., Craessaerts, K., Serneels, S., Checler, F., Annaert, W., Van Broeckhoven, C., De Strooper, B. Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect A-beta secretion and APP C-terminal fragment stability. Hum. Molec. Genet. 10: 1665-1671, 2001. [PubMed: 11487570] [Full Text: https://doi.org/10.1093/hmg/10.16.1665]

  36. De Jonghe, C., Zehr, C., Yager, D., Prada, C.-M., Younkin, S., Hendriks, L., Van Broeckhoven, C., Eckman, C. B. Flemish and Dutch mutations in amyloid beta precursor protein have different effects on amyloid beta secretion. Neurobiol. Dis. 5: 281-286, 1998. [PubMed: 9848098] [Full Text: https://doi.org/10.1006/nbdi.1998.0202]

  37. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., Van Leuven, F. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391: 387-390, 1998. [PubMed: 9450754] [Full Text: https://doi.org/10.1038/34910]

  38. Delabar, J.-M., Goldgaber, D., Lamour, Y., Nicole, A., Huret, J.-L., de Grouchy, J., Brown, P., Gajdusek, D. C., Sinet, P.-M. Beta-amyloid gene duplication in Alzheimer's disease and karyotypically normal Down syndrome. Science 235: 1390-1392, 1987. [PubMed: 2950593] [Full Text: https://doi.org/10.1126/science.2950593]

  39. DeMattos, R. B., Bales, K. R., Cummins, D. J., Paul, S. M., Holtzman, D. M. Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 295: 2264-2267, 2002. [PubMed: 11910111] [Full Text: https://doi.org/10.1126/science.1067568]

  40. DeMattos, R. B., Cirrito, J. R., Parsadanian, M., May, P. C., O'Dell, M. A., Taylor, J. W., Harmony, J. A. K., Aronow, B. J., Bales, K. R., Paul, S. M., Holtzman, D. M. ApoE and clusterin cooperatively suppress A-beta levels and deposition: evidence that ApoE regulates extracellular A-beta metabolism in vivo. Neuron 41: 193-202, 2004. [PubMed: 14741101] [Full Text: https://doi.org/10.1016/s0896-6273(03)00850-x]

  41. Di Fede, G., Catania, M., Morbin, M., Rossi, G., Suardi, S., Mazzoleni, G., Merlin, M., Giovagnoli, A. R., Prioni, S., Erbetta, A., Falcone, C., Gobbi, M., and 11 others. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. Science 323: 1473-1477, 2009. [PubMed: 19286555] [Full Text: https://doi.org/10.1126/science.1168979]

  42. Di Luca, M., Pastorino, L., Bianchetti, A., Perez, J., Vignolo, L. A., Lenzi, G. L., Trabucchi, M., Cattabeni, F., Padovani, A. Differential level of platelet amyloid beta precursor protein isoforms: an early marker for Alzheimer disease. Arch. Neurol. 55: 1195-1200, 1998. [PubMed: 9740113] [Full Text: https://doi.org/10.1001/archneur.55.9.1195]

  43. Dineley, K. T., Xia, X., Bui, D., Sweatt, J. D., Zheng, H. Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha-7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. J. Biol. Chem. 277: 22768-22780, 2002. [PubMed: 11912199] [Full Text: https://doi.org/10.1074/jbc.M200164200]

  44. Dodart, J.-C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., DeLong, C. A., Wu, S., Wu, X., Holtzman, D. M., Paul, S. M. Immunization reverses memory deficits without reducing brain A-beta burden in Alzheimer's disease model. Nature Neurosci. 5: 452-457, 2002. [PubMed: 11941374] [Full Text: https://doi.org/10.1038/nn842]

  45. Dodart, J.-C., Marr, R. A., Koistinaho, M., Gregersen, B. M., Malkani, S., Verma, I. M., Paul, S. M. Gene delivery of human apolipoprotein E alters brain amyloid-beta burden in a mouse model of Alzheimer's disease. Proc. Nat. Acad. Sci. 102: 1211-1216, 2005. [PubMed: 15657137] [Full Text: https://doi.org/10.1073/pnas.0409072102]

  46. Du, H., Guo, L., Fang, F., Chen, D., Sosunov, A. A., McKhann, G. M., Yan, Y., Wang, C., Zhang, H., Molkentin, J. D., Gunn-Moore, F. J., Vonsattel, J. P., Arancio, O., Chen, J. X., Yan, S. D. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nature Med. 14: 1097-1105, 2008. [PubMed: 18806802] [Full Text: https://doi.org/10.1038/nm.1868]

  47. Du, Y., Zhao, Y., Li, C., Zheng, Q., Tian, J., Li, Z., Huang, T. Y., Zhang, W., Xu, H. Inhibition of PKC-delta reduces amyloid-beta levels and reverses Alzheimer disease phenotypes. J. Exp. Med. 215: 1665-1677, 2018. [PubMed: 29739836] [Full Text: https://doi.org/10.1084/jem.20171193]

  48. Duce, J. A., Tsatsanis, A., Cater, M. A., James, S. A., Robb, E., Wikhe, K., Leong, S. L., Perez, K., Johanssen, T., Greenough, M. A., Cho, H. H., Galatis, D., and 9 others. Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell 142: 857-867, 2010. [PubMed: 20817278] [Full Text: https://doi.org/10.1016/j.cell.2010.08.014]

  49. Duff, K., Eckman, C., Zehr, C., Yu, X, Prada, C.-M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M. N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J., Youndkin, S. Increased amyloid-beta-42(43) in brains of mice expressing mutant presenilin 1. Nature 383: 710-713, 1996. [PubMed: 8878479] [Full Text: https://doi.org/10.1038/383710a0]

    (Video) Online Mendelian Inheritance in Man (OMIM): A Genetic Disorder Database

  50. Eckman, C. B., Mehta, N. D., Crook, R., Perez-tur, J., Prihar, G., Pfeiffer, E., Graff-Radford, N., Hinder, P., Yager, D., Zenk, B., Refolo, L. M., Prada, C. M., Younkin, S. G., Hutton, M., Hardy, J. A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A-beta-42(43). Hum. Molec. Genet. 6: 2087-2089, 1997. [PubMed: 9328472] [Full Text: https://doi.org/10.1093/hmg/6.12.2087]

  51. Edwards-Lee, T., Ringman, J. M., Chung, J., Werner, J., Morgan, A., St. George Hyslop, P., Thompson, P., Dutton, R., Mlikotic, A., Rogaeva, E., Hardy, J. An African American family with early-onset Alzheimer disease and an APP (T714I) mutation. Neurology 64: 377-379, 2005. [PubMed: 15668448] [Full Text: https://doi.org/10.1212/01.WNL.0000149761.70566.3E]

  52. Eisele, Y. S., Obermuller, U., Heilbronner, G., Baumann, F., Kaeser, S. A., Wolburg, H., Walker, L. C., Staufenbiel, M., Heikenwalder, M., Jucker, M. Peripherally applied A-beta-containing inoculates induce cerebral beta-amyloidosis. Science 330: 980-982, 2010. [PubMed: 20966215] [Full Text: https://doi.org/10.1126/science.1194516]

  53. El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., Luster, A. D. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Med. 13: 432-438, 2007. [PubMed: 17351623] [Full Text: https://doi.org/10.1038/nm1555]

  54. Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., Ward, P. J. Cleavage of amyloid beta peptide during constitutive processing of its precursor. Science 248: 1122-1124, 1990. [PubMed: 2111583] [Full Text: https://doi.org/10.1126/science.2111583]

  55. Faghihi, M. A., Modarresi, F., Khalil, A. M., Wood, D. E., Sahagan, B. G., Morgan, T. E., Finch, C. E., St. Laurent, G., III, Kenny, P. J., Wahlestedt, C. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nature Med. 14: 723-730, 2008. [PubMed: 18587408] [Full Text: https://doi.org/10.1038/nm1784]

  56. Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E. A., Frosch, M. P., Eckman, C. B., Tanzi, R. E., Selkoe, D. J., Guenette, S. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Nat. Acad. Sci. 100: 4162-4167, 2003. [PubMed: 12634421] [Full Text: https://doi.org/10.1073/pnas.0230450100]

  57. Felsenstein, K. M., Hunihan, L. W., Roberts, S. B. Altered cleavage and secretion of a recombinant beta-APP bearing the Swedish familial Alzheimer's disease mutation. Nature Genet. 6: 251-256, 1994. [PubMed: 8012386] [Full Text: https://doi.org/10.1038/ng0394-251]

  58. Fombonne, J., Rabizadeh, S., Banwait, S., Mehlen, P., Bredesen, D. E. Selective vulnerability in Alzheimer's disease: amyloid precursor protein and p75-NTR interaction. Ann. Neurol. 65: 294-303, 2009. [PubMed: 19334058] [Full Text: https://doi.org/10.1002/ana.21578]

  59. Francis, R., McGrath, G., Zhang, J., Ruddy, D. A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M. C., Parks, A. L., Xu, W., Li, J., Gurney, M., Myers, R. L., Himes, C. S., Hiebsch, R., Ruble, C., Nye, J. S., Curtis, D. aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of beta-APP, and presenilin protein accumulation. Dev. Cell 3: 85-97, 2002. [PubMed: 12110170] [Full Text: https://doi.org/10.1016/s1534-5807(02)00189-2]

  60. Galvan, V., Gorostiza, O. F., Banwait, S., Ataie, M., Logvinova, A. V., Sitaraman, S., Carlson, E., Sagi, S. A., Chevallier, N., Jin, K., Greenberg, D. A., Bredesen, D. E. Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664. Proc. Nat. Acad. Sci. 103: 7130-7135, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 104: 6876 only, 2007. [PubMed: 16641106] [Full Text: https://doi.org/10.1073/pnas.0509695103]

  61. Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., Guido, T., Hagoplan, S., and 22 others. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373: 523-527, 1995. [PubMed: 7845465] [Full Text: https://doi.org/10.1038/373523a0]

    See Also
    Online Mendelian Inheritance in Man (OMIM)Online Mendelian Inheritance in Man (OMIM)Online Mendelian Inheritance in Man (OMIM)Online Mendelian Inheritance in Man (OMIM)

  62. Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J., LeBlanc, A., Smith, D., Rigby, M., Shearman, M. S., Clarke, E. E., Zheng, H., Van Der Ploeg, L. H. T., Ruffolo, S. C., Thornberry, N. A., Xanthoudakis, S., Zamboni, R. J., Roy, S., Nicholson, D. W. Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A-beta peptide formation. Cell 97: 395-406, 1999. [PubMed: 10319819] [Full Text: https://doi.org/10.1016/s0092-8674(00)80748-5]

  63. Glenner, G. G., Wong, C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120: 885-890, 1984. [PubMed: 6375662] [Full Text: https://doi.org/10.1016/s0006-291x(84)80190-4]

  64. Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., Mant, R., Newton, P., Rooke, K., Roques, P., Talbot, C., Pericak-Vance, M., Roses, A., Williamson, R., Rossor, M., Owen, M., Hardy, J. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704-706, 1991. [PubMed: 1671712] [Full Text: https://doi.org/10.1038/349704a0]

  65. Godbolt, A. K., Beck, J. A., Collinge, J. C., Cipolotti, L., Fox, N. C., Rossor, M. N. A second family with familial AD and the V717L APP mutation has a later age at onset. Neurology 66: 611-612, 2006. [PubMed: 16505331] [Full Text: https://doi.org/10.1212/01.WNL.0000197791.53828.2C]

  66. Goldgaber, D., Lerman, M. I., McBride, O. W., Saffiotti, U., Gajdusek, D. C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235: 877-880, 1987. [PubMed: 3810169] [Full Text: https://doi.org/10.1126/science.3810169]

  67. Gotz, J., Chen, F., van Dorpe, J., Nitsch, R. M. Formation of neurofibrillary tangles in P301L tau transgenic mice induced by A-beta42 fibrils. Science 293: 1491-1495, 2001. [PubMed: 11520988] [Full Text: https://doi.org/10.1126/science.1062097]

  68. Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G., Rebeck, G. W., Greenberg, S. M. Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann. Neurol. 49: 697-705, 2001. [PubMed: 11409420] [Full Text: https://doi.org/10.1002/ana.1009]

  69. Greenberg, S. M., Shin, Y., Grabowski, T. J., Cooper, G. E., Rebeck, G. W., Iglesias, S., Chapon, F., Tournier-Lasserve, E., Baron, J.-C. Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation. Neurology 60: 1020-1022, 2003. [PubMed: 12654973] [Full Text: https://doi.org/10.1212/01.wnl.0000050140.10044.a8]

  70. Greenfield, J. P., Leung, L. W., Cai, D., Kaasik, K., Gross, R. S., Rodriguez-Boulan, E., Greengard, P., Xu, H. Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesis. J. Biol. Chem. 277: 12128-12136, 2002. [PubMed: 11823458] [Full Text: https://doi.org/10.1074/jbc.M110009200]

  71. Grimm, M. O. W., Grimm, H. S., Patzold, A. J., Zinser, E. G., Halonen, R., Duering, M., Tschape, J.-A., De Strooper, B., Muller, U., Shen, J., Hartmann, T. Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nature Cell Biol. 7: 1118-1123, 2005. Note: Erratum: Nature Cell Biol. 8: 424 only, 2006. [PubMed: 16227967] [Full Text: https://doi.org/10.1038/ncb1313]

  72. Guo, J.-P., Arai, T., Miklossy, J., McGeer, P. L. Amyloid-beta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. Proc. Nat. Acad. Sci. 103: 1953-1958, 2006. [PubMed: 16446437] [Full Text: https://doi.org/10.1073/pnas.0509386103]

  73. Guyant-Marechal, I., Berger, E., Laquerriere, A., Rovelet-Lecrux, A., Viennet, G., Frebourg, T., Rumbach, L., Campion, D., Hannequin, D. Intrafamilial diversity of phenotype associated with APP duplication. Neurology 71: 1925-1926, 2008. [PubMed: 19047566] [Full Text: https://doi.org/10.1212/01.wnl.0000339400.64213.56]

  74. Guyant-Marechal, L., Rovelet-Lecrux, A., Goumidi, L., Cousin, E., Hannequin, D., Raux, G., Penet, C., Ricard, S., Mace, S., Amouyel, P., Deleuze, J.-F., Frebourg, T., Brice, A., Lambert, J.-C., Campion, D. Variations in the APP gene promoter region and risk of Alzheimer disease. Neurology 68: 684-687, 2007. [PubMed: 17325276] [Full Text: https://doi.org/10.1212/01.wnl.0000255938.33739.46]

  75. Haass, C., Lemere, C. A., Capell, A., Citron, M., Seubert, P., Schenk, D., Lannfelt, L., Selkoe, D. J. The Swedish mutation causes early-onset Alzheimer's disease by beta-secretase cleavage within the secretory pathway. Nature Med. 1: 1291-1296, 1995. [PubMed: 7489411] [Full Text: https://doi.org/10.1038/nm1295-1291]

  76. Hassan, W. M., Merin, D. A., Fonte, V., Link, C. D. AIP-1 ameliorates beta-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model. Hum. Molec. Genet. 18: 2739-2747, 2009. [PubMed: 19414486] [Full Text: https://doi.org/10.1093/hmg/ddp209]

  77. Hendriks, L., van Duijn, C. M., Cras, P., Cruts, M., Van Hul, W., van Harskamp, F., Warren, A., McInnis, M. G., Antonarakis, S. E., Martin, J.-J., Hofman, A., Van Broeckhoven, C. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nature Genet. 1: 218-221, 1992. [PubMed: 1303239] [Full Text: https://doi.org/10.1038/ng0692-218]

  78. Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., Gelpi, E., Halle, A., Korte, M., Latz, E., Golenbock, D. T. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493: 674-678, 2013. [PubMed: 23254930] [Full Text: https://doi.org/10.1038/nature11729]

  79. Hol, E. M., van Dijk, R., Gerez, L., Sluijs, J. A., Hobo, B., Tonk, M. T., de Haan, A., Kamphorst, W., Fischer, D. F., Benne, R., van Leeuwen, F. W. Frameshifted beta-amyloid precursor protein (APP+1) is a secretory protein, and the level of APP+1 in cerebrospinal fluid is linked to Alzheimer pathology. J. Biol. Chem. 278: 39637-39643, 2003. [PubMed: 12900421] [Full Text: https://doi.org/10.1074/jbc.M302295200]

  80. Hou, P., Liu, G., Zhao, Y., Shi, Z., Zheng, Q., Bu, G., Xu, H., Zhang, Y. The role of copper and the copper-related protein CUTA in mediating APP processing and A-beta generation. Neurobiol. Aging 36: 1310-1315, 2015. [PubMed: 25557959] [Full Text: https://doi.org/10.1016/j.neurobiolaging.2014.12.005]

  81. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., Cole, G. Correlative memory deficits, A-beta elevation, and amyloid plaques in transgenic mice. Science 274: 99-103, 1996. [PubMed: 8810256] [Full Text: https://doi.org/10.1126/science.274.5284.99]

  82. Hutter-Paier, B., Huttunen, H. J., Puglielli, L., Eckman, C. B., Kim, D. Y., Hofmeister, A., Moir, R. D., Domnitz, S. B., Frosch, M. P., Windisch, M., Kovacs, D. M. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron 44: 227-238, 2004. Note: Erratum: Neuron 68: 1014, 2010. [PubMed: 15473963] [Full Text: https://doi.org/10.1016/j.neuron.2004.08.043]

  83. Iijima, K., Gatt, A., Iijima-Ando, K. Tau ser262 phosphorylation is critical for A-beta-42-induced tau toxicity in a transgenic Drosophila model of Alzheimer's disease. Hum. Molec. Genet. 19: 2947-2957, 2010. [PubMed: 20466736] [Full Text: https://doi.org/10.1093/hmg/ddq200]

  84. Iijima, K., Liu, H.-P., Chiang, A.-S., Hearn, S. A., Konsolaki, M., Zhong, Y. Dissecting the pathological effects of human A-beta-40 and A-beta-42 in Drosophila: a potential model for Alzheimer's disease. Proc. Nat. Acad. Sci. 101: 6623-6628, 2004. [PubMed: 15069204] [Full Text: https://doi.org/10.1073/pnas.0400895101]

  85. Iijima-Ando, K., Zhao, L., Gatt, A., Shenton, C., Iijima, K. A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration. Hum. Molec. Genet. 19: 1930-1938, 2010. [PubMed: 20159774] [Full Text: https://doi.org/10.1093/hmg/ddq068]

  86. Ittner, A., Chua, S. W., Bertz, J., Volkerling, A., van der Hoven, J., Gladbach, A., Przybyla, M., Bi, M., van Hummel, A., Stevens, C. H., Ippati, S., Suh, L. S., and 9 others. Site-specific phosphorylation of tau inhibits amyloid-beta toxicity in Alzheimer's mice. Science 354: 904-908, 2016. [PubMed: 27856911] [Full Text: https://doi.org/10.1126/science.aah6205]

  87. Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N. P., Gerard, C., Hama, E., Lee, H.-J., Saido, T. C. Metabolic regulation of brain A-beta by neprilysin. Science 292: 1550-1552, 2001. [PubMed: 11375493] [Full Text: https://doi.org/10.1126/science.1059946]

  88. Jankowsky, J. L., Slunt, H. H., Ratovitski, T., Jenkins, N. A., Copeland, N. G., Borchelt, D. R. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomolec. Eng. 17: 157-165, 2001. [PubMed: 11337275] [Full Text: https://doi.org/10.1016/s1389-0344(01)00067-3]

  89. Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., Mount, H. T. J., Nixon, R. A., Mercken, M., Bergeron, C., Fraser, P. E., St. George-Hyslop, P., Westaway, D. A-beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408: 979-982, 2000. [PubMed: 11140685] [Full Text: https://doi.org/10.1038/35050110]

  90. Jarrett, J. T., Berger, E. P., Lansbury, P. T. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 32: 4693-4697, 1993. [PubMed: 8490014] [Full Text: https://doi.org/10.1021/bi00069a001]

  91. Jenkins, E. C., Devine-Gage, E. A., Robakis, N. K., Yao, X.-L., Brown, W. T., Houck, G. E., Jr., Wolfe, G., Ramakrishna, N., Silverman, W. P., Wisniewski, H. M. Fine mapping of an Alzheimer disease-associated gene encoding beta-amyloid protein. Biochem. Biophys. Res. Commun. 151: 1-8, 1988. [PubMed: 3279948] [Full Text: https://doi.org/10.1016/0006-291x(88)90551-7]

  92. Jones, C. T., Morris, S., Yates, C. M., Moffoot, A., Sharpe, C., Brock, D. J. H., St. Clair, D. Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia. Nature Genet. 1: 306-309, 1992. [PubMed: 1307241] [Full Text: https://doi.org/10.1038/ng0792-306]

  93. Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., and 15 others. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488: 96-99, 2012. [PubMed: 22801501] [Full Text: https://doi.org/10.1038/nature11283]

  94. Kamal, A., Almenar-Queralt, A., LeBlanc, J. F., Roberts, E. A., Goldstein, L. S. B. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414: 643-648, 2001. [PubMed: 11740561] [Full Text: https://doi.org/10.1038/414643a]

  95. Kamal, A., Stokin, G. B., Yang, Z., Xia, C.-H., Goldstein, L. S. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28: 449-459, 2000. [PubMed: 11144355] [Full Text: https://doi.org/10.1016/s0896-6273(00)00124-0]

  96. Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., Malinow, R. APP processing and synaptic function. Neuron 37: 925-937, 2003. [PubMed: 12670422] [Full Text: https://doi.org/10.1016/s0896-6273(03)00124-7]

  97. Kamino, K., Orr, H. T., Payami, H., Wijsman, E. M., Alonso, M. E., Pulst, S. M., Anderson, L., O'dahl, S., Nemens, E., White, J. A., Sadovnick, A. D., Ball, M. J., Kaye, J., Warren, A., McInnis, M., Antonarakis, S. E., Korenberg, J. R., Sharma, V., Kukull, W., Larson, E., Heston, L. L., Martin, G. M., Bird, T. D., Schellenberg, G. D. Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. Am. J. Hum. Genet. 51: 998-1014, 1992. [PubMed: 1415269]

  98. Kanekiyo, T., Ban, T., Aritake, K., Huang, Z.-L., Qu, W.-M., Okazaki, I., Mohri, I., Murayama, S., Ozono, K., Taniike, M., Goto, Y., Urade, Y. Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid. Proc. Nat. Acad. Sci. 104: 6412-6417, 2007. [PubMed: 17404210] [Full Text: https://doi.org/10.1073/pnas.0701585104]

    (Video) |OMIM|Online Mendelian inheritance in man|omim

  99. Kaneko, I., Yamada, N., Sakuraba, Y., Kamenosono, M., Tutumi, S. Suppression of mitochondrial succinate dehydrogenase, a primary target of beta-amyloid, and its derivative racemized at ser residue. J. Neurochem. 65: 2585-2593, 1995. [PubMed: 7595555] [Full Text: https://doi.org/10.1046/j.1471-4159.1995.65062585.x]

  100. Kang, D. E., Pietrzik, C. U., Baum, L., Chevallier, N., Merriam, D. E., Kounnas, M. Z., Wagner, S. L., Troncoso, J. C., Kawas, C. H., Katzman, R., Koo, E. H. Modulation of amyloid beta-protein clearance and Alzheimer's disease susceptibility by the LDL receptor-related protein pathway. J. Clin. Invest. 106: 1159-1166, 2000. [PubMed: 11067868] [Full Text: https://doi.org/10.1172/JCI11013]

  101. Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., Muller-Hill, B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733-736, 1987. [PubMed: 2881207] [Full Text: https://doi.org/10.1038/325733a0]

  102. Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., Holtzman, D. M. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326: 1005-1007, 2009. [PubMed: 19779148] [Full Text: https://doi.org/10.1126/science.1180962]

  103. Karlinsky, H., Vaula, G., Haines, J. L., Ridgley, J., Bergeron, C., Mortilla, M., Tupler, R. G., Percy, M. E., Robitaille, Y., Noldy, N. E., Yip, T. C. K., Tanzi, R. E., Gusella, J. F., Becker, R., Berg, J. M., Crapper McLachlan, D. R., St. George-Hyslop, P. H. Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene. Neurology 42: 1445-1453, 1992. Note: Erratum: Neurology 42: 1662 only, 1992. [PubMed: 1520398] [Full Text: https://doi.org/10.1212/wnl.42.8.1445]

  104. Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., Glabe, C. G. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300: 486-489, 2003. [PubMed: 12702875] [Full Text: https://doi.org/10.1126/science.1079469]

  105. Khan, A. A., Mao, X. O., Banwait, S., Jin, K., Greenberg, D. A. Neuroglobin attenuates beta-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo. Proc. Nat. Acad. Sci. 104: 19114-19119, 2007. [PubMed: 18025470] [Full Text: https://doi.org/10.1073/pnas.0706167104]

  106. Kitaguchi, N., Takahashi, Y., Tokushima, Y., Shiojiri, S., Ito, H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331: 530-532, 1988. [PubMed: 2893291] [Full Text: https://doi.org/10.1038/331530a0]

  107. Kojro, E., Gimpl, G., Lammich, S., Marz, W., Fahrenholz, F. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10. Proc. Nat. Acad. Sci. 98: 5815-5820, 2001. [PubMed: 11309494] [Full Text: https://doi.org/10.1073/pnas.081612998]

  108. Korenberg, J. R., Pulst, S.-M., Neve, R. L., West, R. The Alzheimer amyloid precursor protein maps to human chromosome 21 bands q21.105-q21.05. Genomics 5: 124-127, 1989. [PubMed: 2527801] [Full Text: https://doi.org/10.1016/0888-7543(89)90095-5]

  109. Kounnas, M. Z., Moir, R. D., Rebeck, G. W., Bush, A. I., Argraves, W. S., Tanzi, R. E., Hyman, B. T., Strickland, D. K. LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Cell 82: 331-340, 1995. [PubMed: 7543026] [Full Text: https://doi.org/10.1016/0092-8674(95)90320-8]

  110. Krezowski, J., Knudson, D., Ebeling, C., Pitstick, R., Giri, R. K., Schenk, D., Westaway, D., Younkin, L., Younkin, S. G., Ashe, K. H., Carlson, G. A. Identification of loci determining susceptibility to the lethal effects of amyloid precursor protein transgene overexpression. Hum. Molec. Genet. 13: 1989-1997, 2004. [PubMed: 15254013] [Full Text: https://doi.org/10.1093/hmg/ddh210]

  111. Kumar-Singh, S., De Jonghe, C., Cruts, M., Kleinert, R., Wang, R., Mercken, M., De Strooper, B., Vanderstichele, H., Lofgren, A., Vanderhoeven, I., Backhovens, H., Vanmechelen, E., Kroisel, P. M., Van Broeckhoven, C. Nonfibrillar diffuse amyloid deposition due to a gamma-42-secretase site mutation points to an essential role for N-truncated A-beta-42 in Alzheimer's disease. Hum. Molec. Genet. 9: 2589-2598, 2000. [PubMed: 11063718] [Full Text: https://doi.org/10.1093/hmg/9.18.2589]

  112. LaFerla, F. M., Tinkle, B. T., Bieberich, C. J., Haudenschild, C. C., Jay, G. The Alzheimer's A-beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice. Nature Genet. 9: 21-30, 1995. [PubMed: 7704018] [Full Text: https://doi.org/10.1038/ng0195-21]

  113. Lashuel, H. A., Hartley, D., Petre, B. M., Walz, T., Lansbury, P. T., Jr. Amyloid pores from pathogenic mutations. Nature 418: 291 only, 2002. [PubMed: 12124613] [Full Text: https://doi.org/10.1038/418291a]

  114. Lauren, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., Strittmatter, S. M. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457: 1128-1132, 2009. [PubMed: 19242475] [Full Text: https://doi.org/10.1038/nature07761]

  115. Lazarov, O., Robinson, J., Tang, Y.-P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M.-Y., Hersh, L. B., Sapolsky, R. M., Mirnics, K., Sisodia, S. S. Environmental enrichment reduces A-beta levels and amyloid deposition in transgenic mice. Cell 120: 701-713, 2005. [PubMed: 15766532] [Full Text: https://doi.org/10.1016/j.cell.2005.01.015]

  116. Lee, E. B., Zhang, B., Liu, K., Greenbaum, E. A., Doms, R. W., Trojanowski, J. Q., Lee, V. M.-Y. BACE overexpression alters the subcellular processing of APP and inhibits A-beta deposition in vivo. J. Cell Biol. 168: 291-302, 2005. [PubMed: 15642747] [Full Text: https://doi.org/10.1083/jcb.200407070]

  117. Lee, M.-H., Siddoway, B., Kaeser, G. E., Segota, I., Rivera, R., Romanow, W. J., Liu, C. S., Park, C., Kennedy, G., Long, T., Chun, J. Somatic APP gene recombination in Alzheimer's disease and normal neurons. Nature 563: 639-645, 2018. Note: Erratum: Nature 566: E6, 2019. Electronic Article. [PubMed: 30464338] [Full Text: https://doi.org/10.1038/s41586-018-0718-6]

  118. Lehman, E. J. H., Kulnane, L. S., Gao, Y., Petriello, M. C., Pimpis, K. M., Younkin, L., Dolios, G., Wang, R., Younkin, S. G., Lamb, B. T. Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse. Hum. Molec. Genet. 12: 2949-2956, 2003. [PubMed: 14506131] [Full Text: https://doi.org/10.1093/hmg/ddg322]

  119. Leissring, M. A., Farris, W., Chang, A. Y., Walsh, D. M., Wu, X., Sun, X., Frosch, M. P., Selkoe, D. J. Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40: 1087-1093, 2003. [PubMed: 14687544] [Full Text: https://doi.org/10.1016/s0896-6273(03)00787-6]

  120. Lesne, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., Ashe, K. H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440: 352-357, 2006. [PubMed: 16541076] [Full Text: https://doi.org/10.1038/nature04533]

  121. Levy, E., Carman, M. D., Fernandez-Madrid, I. J., Power, M. D., Lieberburg, I., van Duinen, S. G., Bots, G. T. A. M., Luyendijk, W., Frangione, B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248: 1124-1126, 1990. [PubMed: 2111584] [Full Text: https://doi.org/10.1126/science.2111584]

  122. Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., Eckman, C., Hardy, J., Hutton, M., McGowan, E. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293: 1487-1491, 2001. [PubMed: 11520987] [Full Text: https://doi.org/10.1126/science.1058189]

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  123. Liu, Q., Zerbinatti, C. V., Zhang, J., Hoe, H.-S., Wang, B., Cole, S. L., Herz, J., Muglia, L., Bu, G. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron 56: 66-78, 2007. [PubMed: 17920016] [Full Text: https://doi.org/10.1016/j.neuron.2007.08.008]

  124. Lleo, A., Berezovska, O., Herl, L., Raju, S., Deng, A., Bacskai, B. J., Frosch, M. P., Irizarry, M., Hyman, B. T. Nonsteroidal anti-inflammatory drugs lower A-beta-42 and change presenilin 1 conformation. Nature Med. 10: 1065-1066, 2004. [PubMed: 15448688] [Full Text: https://doi.org/10.1038/nm1112]

  125. Loane, D. J., Pocivavsek, A., Moussa, C. E.-H., Thompson, R., Matsuoka, Y., Faden, A. I., Rebeck, G. W., Burns, M. P. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nature Med. 15: 377-379, 2009. [PubMed: 19287391] [Full Text: https://doi.org/10.1038/nm.1940]

  126. Lorenzo, A., Yuan, M., Zhang, Z., Paganetti, P. A., Sturchler-Pierrat, C., Staufenbiel, M., Mautino, J., Vigo, F. S., Sommer, B., Yankner, B. A. Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease. Nature Neurosci. 3: 460-464, 2000. [PubMed: 10769385] [Full Text: https://doi.org/10.1038/74833]

  127. Lovett, M., Goldgaber, D., Ashley, P., Cox, D. R., Gajdusek, D. C., Epstein, C. J. The mouse homolog of the human amyloid beta protein (AD-AP) gene is located on the distal end of mouse chromosome 16: further extension of the homology between human chromosome 21 and mouse chromosome 16. Biochem. Biophys. Res. Commun. 144: 1069-1075, 1987. [PubMed: 3555492] [Full Text: https://doi.org/10.1016/s0006-291x(87)80073-6]

  128. Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., Trinchese, F., Liu, S., and 9 others. ABAD directly links A-beta to mitochondrial toxicity in Alzheimer's disease. Science 304: 448-452, 2004. [PubMed: 15087549] [Full Text: https://doi.org/10.1126/science.1091230]

  129. Mant, R., Asherson, P., Gill, M., McGuffin, P., Owen, M. Schizophrenia scepticism. (Letter) Nature Genet. 2: 12 only, 1992. [PubMed: 1303244] [Full Text: https://doi.org/10.1038/ng0992-12]

  130. Maruyama, K., Tomita, T., Shinozaki, K., Kume, H., Asada, H., Saido, T. C., Ishiura, S., Iwatsubo, T., Obata, K. Familial Alzheimer's disease-linked mutations at val717 of amyloid precursor protein are specific for the increased secretion of A-beta-42(43). Biochem. Biophys. Res. Commun. 227: 730-735, 1996. [PubMed: 8886002] [Full Text: https://doi.org/10.1006/bbrc.1996.1577]

  131. Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., Beyreuther, K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Nat. Acad. Sci. 82: 4245-4249, 1985. [PubMed: 3159021] [Full Text: https://doi.org/10.1073/pnas.82.12.4245]

  132. McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., Jansen, K., DeLucia, M., Lin, W.-L., Dolios, G., Wang, R., Eckman, C. B., Dickson, D. W., Hutton, M., Hardy, J., Golde, T. A-beta-42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47: 191-199, 2005. [PubMed: 16039562] [Full Text: https://doi.org/10.1016/j.neuron.2005.06.030]

  133. Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., Vigouret, J.-M., Paganetti, P., Walsh, D. M., Mathews, P. M., Ghiso, J., Staufenbiel, M., Walker, L. C., Jucker, M. Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 313: 1781-1784, 2006. [PubMed: 16990547] [Full Text: https://doi.org/10.1126/science.1131864]

  134. Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., Hyman, B. T. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 451: 720-724, 2008. [PubMed: 18256671] [Full Text: https://doi.org/10.1038/nature06616]

  135. Meziane, H., Dodart, J.-C., Mathis, C., Little, S., Clemens, J., Paul, S. M., Ungerer, A. Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice. Proc. Nat. Acad. Sci. 95: 12683-12688, 1998. [PubMed: 9770546] [Full Text: https://doi.org/10.1073/pnas.95.21.12683]

  136. Miravalle, L., Tokuda, T., Chiarle, R., Giaccone, G., Bugiani, O., Tagliavini, F., Frangione, B., Ghiso, J. Substitutions at codon 22 of Alzheimer's A-beta peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J. Biol. Chem. 275: 27110-27116, 2000. [PubMed: 10821838] [Full Text: https://doi.org/10.1074/jbc.M003154200]

  137. Mitchell, J. C., Ariff, B. B., Yates, D. M., Lau, K.-F., Perkinton, M. S., Rogelj, B., Stephenson, J. D., Miller, C. C. J., McLoughlin, D. M. X11-beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice. Hum. Molec. Genet. 18: 4492-4500, 2009. [PubMed: 19744962] [Full Text: https://doi.org/10.1093/hmg/ddp408]

  138. Morelli, L., Llovera, R., Gonzalez, S. A., Affranchino, J. L., Prelli, F., Frangione, B., Ghiso, J., Castano, E. M. Differential degradation of amyloid-beta genetic variants associated with hereditary dementia or stroke by insulin-degrading enzyme. J. Biol. Chem. 278: 23221-23226, 2003. [PubMed: 12695513] [Full Text: https://doi.org/10.1074/jbc.M300276200]

  139. Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C., Hardy, J., Duff, K., Jantzen, P., DiCarlo, G., Wilcock, D., Connor, K., Hatcher, J., Hope, C., Gordon, M., Arendash, G. W. A-beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408: 982-985, 2000. Note: Erratum Nature 412: 660 only, 2001. [PubMed: 11140686] [Full Text: https://doi.org/10.1038/35050116]

  140. Mueller-Steiner, S., Zhou, Y., Arai, H., Roberson, E. D., Sun, B., Chen, J., Wang, X., Yu, G., Esposito, L., Mucke, L., Gan, L. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron 51: 703-714, 2006. [PubMed: 16982417] [Full Text: https://doi.org/10.1016/j.neuron.2006.07.027]

  141. Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., Lannfelt, L. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nature Genet. 1: 345-347, 1992. [PubMed: 1302033] [Full Text: https://doi.org/10.1038/ng0892-345]

  142. Multhaup, G., Schlicksupp, A., Hesse, L., Beher, D., Ruppert, T., Masters, C. L., Beyreuther, K. The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper (I). Science 271: 1406-1409, 1996. [PubMed: 8596911] [Full Text: https://doi.org/10.1126/science.271.5254.1406]

  143. Munter, L.-M., Botev, A., Richter, L., Hildebrand, P. W., Althoff, V., Weise, C., Kaden, D., Multhaup, G. Aberrant amyloid precursor protein (APP) processing in hereditary forms of Alzheimer disease caused by APP familial Alzheimer disease mutations can be rescued by mutations in the APP GxxxG motif. J. Biol. Chem. 285: 21636-21643, 2010. [PubMed: 20452985] [Full Text: https://doi.org/10.1074/jbc.M109.088005]

  144. Munter, L.-M., Voigt, P., Harmeier, A., Kaden, D., Gottschalk, K. E., Weise, C., Pipkorn, R., Schaefer, M., Langosch, D., Multhaup, G. GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42. EMBO J. 26: 1702-1712, 2007. [PubMed: 17332749] [Full Text: https://doi.org/10.1038/sj.emboj.7601616]

  145. Murdoch, G. H., Manuelidis, L., Kim, J. H., Manuelidis, E. E. Beta-amyloid gene dosage in Alzheimer's disease. Nucleic Acids Res. 16: 357, 1988. [PubMed: 3277160] [Full Text: https://doi.org/10.1093/nar/16.1.357]

  146. Muresan, Z., Muresan, V. A phosphorylated, carboxy-terminal fragment of beta-amyloid precursor protein localizes to the splicing factor compartment. Hum. Molec. Genet. 13: 475-488, 2004. [PubMed: 14722157] [Full Text: https://doi.org/10.1093/hmg/ddh054]

  147. Murrell, J., Farlow, M., Ghetti, B., Benson, M. D. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254: 97-99, 1991. [PubMed: 1925564] [Full Text: https://doi.org/10.1126/science.1925564]

    (Video) Online Mendelian Inheritance in Man (ClinGen Biocurator Working Group)

  148. Murrell, J. R., Hake, A. M., Quaid, K. A., Farlow, M. R., Ghetti, B. Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene. Arch. Neurol. 57: 885-887, 2000. [PubMed: 10867787] [Full Text: https://doi.org/10.1001/archneur.57.6.885]

  149. Narita, M., Holtzman, D. M., Schwartz, A. L., Bu, G. Alpha 2-macroglobulin complexes with and mediates the endocytosis of beta-amyloid peptide via cell surface low-density lipoprotein receptor-related protein. J. Neurochem. 69: 1904-1911, 1997. [PubMed: 9349534] [Full Text: https://doi.org/10.1046/j.1471-4159.1997.69051904.x]

  150. Naruse, S., Igarashi, S., Kobayashi, H., Aoki, K., Inuzuka, T., Kaneko, K., Shimizu, T., Iihara, K., Kojima, T., Miyatake, T., Tsuji, S. Mis-sense mutation val-to-ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. (Letter) Lancet 337: 978-979, 1991. [PubMed: 1678058] [Full Text: https://doi.org/10.1016/0140-6736(91)91612-x]

  151. Netzer, W. J., Dou, F., Cai, D., Veach, D., Jean, S., Li, Y., Bornmann, W. G., Clarkson, B., Xu, H., Greengard, P. Gleevec inhibits beta-amyloid production but not notch cleavage. Proc. Nat. Acad. Sci. 100: 12444-12449, 2003. [PubMed: 14523244] [Full Text: https://doi.org/10.1073/pnas.1534745100]

  152. Ni, Y., Zhao, X., Bao, G., Zou, L., Teng, L., Wang, Z., Song, M., Xiong, J., Bai, Y., Pai, G. Activation of beta-2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nature Med. 12: 1390-1396, 2006. [PubMed: 17115048] [Full Text: https://doi.org/10.1038/nm1485]

  153. Nikolaev, A., McLaughlin, T., O'Leary, D. D. M., Tessier-Lavigne, M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457: 981-989, 2009. [PubMed: 19225519] [Full Text: https://doi.org/10.1038/nature07767]

  154. Nilsberth, C., Westlind-Danielsson, A., Eckman, C. B., Condron, M. M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D. B., Younkin, S. G., Naslund, J., Lannfelt, L. The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced amyloid-beta protofibril formation. Nature Neurosci. 4: 887-893, 2001. [PubMed: 11528419] [Full Text: https://doi.org/10.1038/nn0901-887]

  155. Nussbaum, J. M., Schilling, S., Cynis, H., Silva, A., Swanson, E., Wangsanut, T., Tayler, K., Wiltgen, B., Hatami, A., Ronicke, R., Reymann, K., Hutter-Paier, B., Alexandru, A., Jagla, W., Graubner, S., Glabe, C. G., Demuth, H.-U., Bloom, G. S. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-beta. Nature 485: 651-655, 2012. [PubMed: 22660329] [Full Text: https://doi.org/10.1038/nature11060]

  156. Obici, L., Demarchi, A., de Rosa, G., Bellotti, V., Marciano, S., Donadei, S., Arbustini, E., Palladini, G., Diegoli, M., Genovese, E., Ferrari, G., Coverlizza, S., Merlini, G. A novel A-beta-PP mutation exclusively associated with cerebral amyloid angiopathy. Ann. Neurol. 58: 639-644, 2005. [PubMed: 16178030] [Full Text: https://doi.org/10.1002/ana.20571]

  157. Oesch, B., Westaway, D., Walchli, M., McKinley, M. P., Kent, S. B. H., Aebersold, R., Barry, R. A., Tempst, P., Teplow, D. B., Hood, L. E., Prusiner, S. B., Weissmann, C. A cellular gene encodes scrapie PrP 27-30 protein. Cell 40: 735-746, 1985. [PubMed: 2859120] [Full Text: https://doi.org/10.1016/0092-8674(85)90333-2]

  158. Ohno, M., Sametsky, E. A., Younkin, L. H., Oakley, H., Younkin, S. G., Citron, M., Vassar, R., Disterhoft, J. F. BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron 41: 27-33, 2004. [PubMed: 14715132] [Full Text: https://doi.org/10.1016/s0896-6273(03)00810-9]

  159. Pardossi-Piquard, R., Dunys, J., Kawarai, T., Sunyach, C., Alces da Costa, C. A., Vincent, B., Sevalle, J., Pimplikar, S., St. George-Hyslop, P., Checler, F. Response to correspondence: Pardossi-Piquard et al., 'Presenilin-dependent transcriptional control of the A-beta-degrading enzyme neprilysin by intracellular domains of beta-APP and APLP.' Neuron 53: 483-486, 2007. [PubMed: 17296550] [Full Text: https://doi.org/10.1016/j.neuron.2007.01.024]

  160. Pardossi-Piquard, R., Petit, A., Kawarai, T., Sunyach, C., Alves da Costa, C., Vincent, B., Ring, S., D'Adamio, L., Shen, J., Muller, U., St. George Hyslop, P., Checler, F. Presenilin-dependent transcriptional control of the A-beta-degrading enzyme neprilysin by intracellular domains of beta-APP and APLP. Neuron 46: 541-554, 2005. [PubMed: 15944124] [Full Text: https://doi.org/10.1016/j.neuron.2005.04.008]

  161. Pasalar, P., Najmabadi, H., Noorian, A. R., Moghimi, B., Jannati, A., Soltanzadeh, A., Krefft, T., Crook, R., Hardy, J. An Iranian family with Alzheimer's disease caused by a novel APP mutation (thr714-to-ala). Neurology 58: 1574-1575, 2002. [PubMed: 12034808] [Full Text: https://doi.org/10.1212/wnl.58.10.1574]

  162. Paschkowsky, S., Hamze, M., Oestereich, F., Munter, L. M. Alternative processing of the amyloid precursor protein family by rhomboid protease RHBDL4. J. Biol. Chem. 291: 21903-21912, 2016. [PubMed: 27563067] [Full Text: https://doi.org/10.1074/jbc.M116.753582]

  163. Paschkowsky, S., Recinto, S. J., Young, J. C., Bondar, A.-N., Munter, L. M. Membrane cholesterol as regulator of human rhomboid protease RHBDL4. J. Biol. Chem. 293: 15556-15568, 2018. [PubMed: 30143535] [Full Text: https://doi.org/10.1074/jbc.RA118.002640]

  164. Pastorino, L., Sun, A., Lu, P.-J., Zhou, X. Z., Balastik, M., Finn, G., Wulf, G., Lim, J., Li, S.-H., Li, X., Xia, W., Nicholson, L. K., Lu, K. P. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440: 528-534, 2006. Note: Erratum: Nature 446: 342 only, 2007. [PubMed: 16554819] [Full Text: https://doi.org/10.1038/nature04543]

  165. Patterson, D., Gardiner, K., Kao, F.-T., Tanzi, R., Watkins, P., Gusella, J. F. Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21. Proc. Nat. Acad. Sci. 85: 8266-8270, 1988. [PubMed: 2973063] [Full Text: https://doi.org/10.1073/pnas.85.21.8266]

  166. Peacock, M. L., Murman, D. L., Sima, A. A. F., Warren, J. T., Jr., Roses, A. D., Fink, J. K. Novel amyloid precursor protein gene mutation (codon 665asp) in a patient with late-onset Alzheimer disease. Ann. Neurol. 35: 432-438, 1994. [PubMed: 8154870] [Full Text: https://doi.org/10.1002/ana.410350410]

  167. Petersen, R. C., Doody, R., Kurz, A., Mohs, R. C., Morris, J. C., Rabins, P. V., Ritchie, K., Rossor, M., Thal, L., Winblad, B. Current concepts in mild cognitive impairment. Arch. Neurol. 58: 1985-1992, 2001. [PubMed: 11735772] [Full Text: https://doi.org/10.1001/archneur.58.12.1985]

  168. Petkova, A. T., Leapman, R. D., Guo, Z., Yau, W.-M., Mattson, M. P., Tycko, R. Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils. Science 307: 262-265, 2005. [PubMed: 15653506] [Full Text: https://doi.org/10.1126/science.1105850]

  169. Pfeifer, M., Boncristiano, S., Bondolfi, L., Stalder, A., Deller, T., Staufenbiel, M., Mathews, P. M., Jucker, M. Cerebral hemorrhage after passive anti-A-beta immunotherapy. Science 298: 1379 only, 2002. [PubMed: 12434053] [Full Text: https://doi.org/10.1126/science.1078259]

  170. Phiel, C. J., Wilson, C. A., Lee, V. M.-Y., Klein, P. S. GSK-3-alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 423: 435-439, 2003. [PubMed: 12761548] [Full Text: https://doi.org/10.1038/nature01640]

  171. Podlisny, M. B., Lee, G., Selkoe, D. J. Gene dosage of the amyloid beta precursor protein in Alzheimer's disease. Science 238: 669-671, 1987. [PubMed: 2960019] [Full Text: https://doi.org/10.1126/science.2960019]

  172. Ponte, P., Gonzalez-DeWhitt, P., Schilling, J., Miller, J., Hsu, D., Greenburg, B., Davis, K., Wallace, W., Lieberburg, I., Fuller, F., Cordell, B. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 331: 525-527, 1988. [PubMed: 2893289] [Full Text: https://doi.org/10.1038/331525a0]

  173. Postina, R., Schroeder, A., Dewachter, I., Bohl, J., Schmitt, U., Kojro, E., Prinzen, C., Endres, K., Hiemke, C., Blessing, M., Flamez, P., Dequenne, A., Godaux, E., van Leuven, F., Fahrenholz, F. A disintegrin-met alloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J. Clin. Invest. 113: 1456-1464, 2004. Note: Erratum: J. Clin. Invest. 114: 598 only, 2004. [PubMed: 15146243] [Full Text: https://doi.org/10.1172/JCI20864]

  174. Puglielli, L., Konopka, G., Pack-Chung, E., MacKenzie Ingano, L. A., Berezovska, O., Hyman, B. T., Chang, T. Y., Tanzi, R. E., Kovacs, D. M. Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nature Cell Biol. 3: 905-912, 2001. [PubMed: 11584272] [Full Text: https://doi.org/10.1038/ncb1001-905]

  175. Ranganathan, S., Noyes, N. C., Migliorini, M., Winkles, J. A., Battey, F. D., Hyman, B. T., Smith, E., Yepes, M., Mikhailenko, I., Strickland, D. K. LRAD3, a novel low-density lipoprotein receptor family member that modulates amyloid precursor protein trafficking. J. Neurosci. 31: 10836-10846, 2011. [PubMed: 21795536] [Full Text: https://doi.org/10.1523/JNEUROSCI.5065-10.2011]

  176. Raux, G., Guyant-Marechal, L., Martin, C., Bou, J., Penet, C., Brice, A., Hannequin, D., Frebourg, T., Campion, D. Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. (Letter) J. Med. Genet. 42: 793-795, 2005. [PubMed: 16033913] [Full Text: https://doi.org/10.1136/jmg.2005.033456]

  177. Reddy, P. H., McWeeney, S., Park, B. S., Manczak, M., Gutala, R. V., Partovi, D., Jung, Y., Yau, V., Searles, R., Mori, M., Quinn, J. Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease. Hum. Molec. Genet. 13: 1225-1240, 2004. [PubMed: 15115763] [Full Text: https://doi.org/10.1093/hmg/ddh140]

  178. Revesz, T., Holton, J. L., Lashley, T., Plant, G., Frangione, B., Rostagno, A., Ghiso, J. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropath. 118: 115-130, 2009. Note: Erratum: Acta Neuropath. 118: 321 only, 2009. [PubMed: 19225789] [Full Text: https://doi.org/10.1007/s00401-009-0501-8]

  179. Rice, H. C., de Malmazet, D., Schreurs, A., Frere, S., Van Molle, I., Volkov, A. N., Creemers, E., Vertkin, I., Nys, J., Ranaivoson, F. M., Comoletti, D., Savas, J. N., Remaut, H., Balschun, D., Wierda, K. D., Slutsky, I., Farrow, K., De Strooper, B., de Wit, J. Secreted amyloid-beta precursor protein functions as a GABABR1a ligand to modulate synaptic transmission. Science 363: eaao4827, 2019. Note: Electronic Article. [PubMed: 30630900] [Full Text: https://doi.org/10.1126/science.aao4827]

  180. Robakis, N. K., Ramakrishna, N., Wolfe, G., Wisniewski, H. M. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc. Nat. Acad. Sci. 84: 4190-4194, 1987. Note: Erratum: Proc. Nat. Acad. Sci. 84: 7221 only, 1987. [PubMed: 3035574] [Full Text: https://doi.org/10.1073/pnas.84.12.4190]

  181. Robakis, N. K., Wisniewski, H. M., Jenkins, E. C., Devine-Gage, E. A., Houck, G. E., Yao, X.-L., Ramakrishna, N., Wolfe, G., Silverman, W. P., Brown, W. T. Chromosome 21q21 sublocalisation of gene encoding beta-amyloid peptide in cerebral vessels and neuritic (senile) plaques of people with Alzheimer disease and Down syndrome. (Letter) Lancet 329: 384-385, 1987. Note: Originally Volume 1. [PubMed: 2880184] [Full Text: https://doi.org/10.1016/s0140-6736(87)91754-5]

  182. Roberds, S. L., Anderson, J., Basi, G., Bienkowski, M. J., Branstetter, D. G., Chen, K. S., Freedman, S. B., Frigon, N. L., Games, D., Hu, K., Johnson-Wood, K., Kappenman, K. E., and 20 others. BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum. Molec. Genet. 10: 1317-1324, 2001. [PubMed: 11406613] [Full Text: https://doi.org/10.1093/hmg/10.12.1317]

  183. Rossi, G., Giaccone, G., Maletta, R., Morbin, M., Capobianco, R., Mangieri, M., Giovagnoli, A. R., Bizzi, A., Tomaino, C., Perri, M., Di Natale, M., Tagliavini, F., Bugiani, O., Bruni, A. C. A family with Alzheimer disease and strokes associated with the A713T mutation of the APP gene. Neurology 63: 910-912, 2004. [PubMed: 15365148] [Full Text: https://doi.org/10.1212/01.wnl.0000137048.80666.86]

  184. Rovelet-Lecrux, A., Hannequin, D., Raux, G., Le Meur, N., Laquerriere, A., Vital, A., Dumanchin, C., Feuillette, S., Brice, A., Vercelletto, M., Dubas, F., Frebourg, T., Campion, D. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nature Genet. 38: 24-26, 2006. [PubMed: 16369530] [Full Text: https://doi.org/10.1038/ng1718]

  185. Saito, T., Iwata, N., Tsubuki, S., Takaki, Y., Takano, J., Huang, S.-M., Suemoto, T., Higuchi, M., Saido, T. C. Somatostatin regulates brain amyloid beta-peptide A-beta-42 through modulation of proteolytic degradation. Nature Med. 11: 434-439, 2005. [PubMed: 15778722] [Full Text: https://doi.org/10.1038/nm1206]

  186. Sandbrink, R., Masters, C. L., Beyreuther, K. Beta A4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons. J. Biol. Chem. 269: 1510-1517, 1994. [PubMed: 8288617]

  187. Schellenberg, G. D., Anderson, L., O'dahl, S., Wisjman, E. M., Sadovnick, A. D., Ball, M. J., Larson, E. B., Kukull, W. A., Martin, G. M., Roses, A. D., Bird, T. D. APP(717), APP(693), and PRIP gene mutations are rare in Alzheimer disease. Am. J. Hum. Genet. 49: 511-517, 1991. [PubMed: 1679288]

  188. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., and 13 others. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400: 173-177, 1999. [PubMed: 10408445] [Full Text: https://doi.org/10.1038/22124]

  189. Schenk, D. Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. Nature Rev. Neurosci. 3: 824-828, 2002. [PubMed: 12360327] [Full Text: https://doi.org/10.1038/nrn938]

  190. Schilling, S., Zeitschel, U., Hoffmann, T., Heiser, U., Francke, M., Kehlen, A., Holzer, M., Hutter-Paier, B., Prokesch, M., Windisch, M., Jagla, W., Schlenzig, D., Lindner, C., Rudolph, T., Reuter, G., Cynis, H., Montag, D., Demuth, H.-U., Rossner, S. Glutaminyl cyclase inhibition attenuates pyroglutamate A-beta and Alzheimer's disease-like pathology. Nature Med. 14: 1106-1111, 2008. [PubMed: 18836460] [Full Text: https://doi.org/10.1038/nm.1872]

  191. Schmaier, A. H., Dahl, L. D., Rozemuller, A. J. M., Roos, R. A. C., Wagner, S. L., Chung, R., Van Nostrand, W. E. Protease nexin-2/amyloid-beta protein precursor: a tight-binding inhibitor of coagulation factor IXa. J. Clin. Invest. 92: 2540-2545, 1993. [PubMed: 8227367] [Full Text: https://doi.org/10.1172/JCI116863]

  192. Schobel, S., Neumann, S., Hertweck, M., Dislich, B., Kuhn, P.-H., Kremmer, E., Seed, B., Baumeister, R., Haass, C., Lichtenthaler, S. F. A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. J. Biol. Chem. 283: 14257-14268, 2008. [PubMed: 18353773] [Full Text: https://doi.org/10.1074/jbc.M801531200]

  193. Selkoe, D. J., Bell, D. S., Podlisny, M. B., Price, D. L., Cork, L. C. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science 235: 873-877, 1987. [PubMed: 3544219] [Full Text: https://doi.org/10.1126/science.3544219]

  194. Senior, K. Alzheimer's and prion disease: do they share a pathogenic mechanism? Lancet 355: 1434 only, 2000.

  195. Sennvik, K., Fastbom, J., Blomberg, M., Wahlund, L.-O., Winblad, B., Benedikz, E. Levels of alpha- and beta-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients. Neurosci. Lett. 278: 169-172, 2000. [PubMed: 10653020] [Full Text: https://doi.org/10.1016/s0304-3940(99)00929-5]

  196. Simons, A., Ruppert, T., Schmidt, C., Schlicksupp, A., Pipkorn, R., Reed, J., Masters, C. L., Whiter, A. R., Cappai, R., Beyreuther, K., Bayer, T. A., Multhaup, G. Evidence for a copper-binding superfamily of the amyloid precursor protein. Biochemistry 41: 9310-9320, 2002. [PubMed: 12135352] [Full Text: https://doi.org/10.1021/bi0258647]

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  197. Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., Simons, K. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Nat. Acad. Sci. 95: 6460-6464, 1998. [PubMed: 9600988] [Full Text: https://doi.org/10.1073/pnas.95.11.6460]

  198. Sisodia, S. S., Gallagher, M. A role for the beta-amyloid precursor protein in memory? Proc. Nat. Acad. Sci. 95: 12074-12076, 1998. [PubMed: 9770440] [Full Text: https://doi.org/10.1073/pnas.95.21.12074]

  199. Smith, R. P., Higuchi, D. A., Broze, G. J., Jr. Platelet coagulation factor XI(a)-inhibitor: a form of Alzheimer amyloid precursor protein. Science 248: 1126-1128, 1990. [PubMed: 2111585] [Full Text: https://doi.org/10.1126/science.2111585]

  200. St. George-Hyslop, P., Crapper McLachlan, D., Tsuda, T., Rogaev, E. Alzheimer's disease and possible gene interaction. (Letter) Science 263: 537 only, 1994. Note: Erratum: Science 263: 904 only, 1994. [PubMed: 8290965] [Full Text: https://doi.org/10.1126/science.8290965]

  201. St. George-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., Neve, R. L., Pollen, D., Drachman, D., Growdon, J., Cupples, L. A., Nee, L., Myers, R. H., O'Sullivan, D., Watkins, P. C., Amos, J. A., Deutsch, C. K., Bodfish, J. W., Kinsbourne, M., Feldman, R. G., Bruni, A., Amaducci, L., Foncin, J.-F., Gusella, J. F. Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease. Science 238: 664-666, 1987. [PubMed: 2890206] [Full Text: https://doi.org/10.1126/science.2890206]

  202. Stieren, E. S., El Ayadi, A., Xiao, Y., Siller, E., Landsverk, M. L., Oberhauser, A. F., Barral, J. M., Boehning, D. Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein. J. Biol. Chem. 286: 35689-35698, 2011. [PubMed: 21852239] [Full Text: https://doi.org/10.1074/jbc.M111.243147]

  203. Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Paganetti, P. A., Waridel, C., Calhoun, M. E., Jucker, M., Probst, A., Staufenbiel, M., Sommer, B. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Nat. Acad. Sci. 94: 13287-13292, 1997. [PubMed: 9371838] [Full Text: https://doi.org/10.1073/pnas.94.24.13287]

  204. Sugarman, M. C., Yamasaki, T. R., Oddo, S., Echegoyen, J. C., Murphy, M. P., Golde, T. E., Jannatipour, M., Leissring, M. A., LaFerla, F. M. Inclusion body myositis-like phenotype induced by transgenic overexpression of beta-APP in skeletal muscle. Proc. Nat. Acad. Sci. 99: 6334-6339, 2002. [PubMed: 11972038] [Full Text: https://doi.org/10.1073/pnas.082545599]

  205. Suzuki, N., Cheung, T. T., Cai, X.-D., Odaka, A., Otvos, L., Jr., Eckman, C., Golde, T. E., Younkin, S. G. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta-APP-717) mutants. Science 264: 1336-1340, 1994. [PubMed: 8191290] [Full Text: https://doi.org/10.1126/science.8191290]

  206. Tagawa, K., Kunishita, T., Maruyama, K., Yoshikawa, K., Kominami, E., Tsuchiya, T., Suzuki, K., Tabira, T., Sugita, H., Ishiura, S. Alzheimer's disease amyloid beta-clipping enzyme (APP secretase): identification, purification, and characterization of the enzyme. Biochem. Biophys. Res. Commun. 177: 377-387, 1991. [PubMed: 1645961] [Full Text: https://doi.org/10.1016/0006-291x(91)91994-n]

  207. Takahashi, M., Dore, S., Ferris, C. D., Tomita, T., Sawa, A., Wolosker, H., Borchelt, D. R., Iwatsubo, T., Kim, S.-H., Thinakaran, G., Sisodia, S. S., Snyder, S. H. Amyloid precursor proteins inhibit heme oxygenase activity and augment neurotoxicity in Alzheimer's disease. Neuron 28: 461-473, 2000. [PubMed: 11144356] [Full Text: https://doi.org/10.1016/s0896-6273(00)00125-2]

  208. Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G., Iwatsubo, T. The role of presenilin cofactors in the gamma-secretase complex. Nature 422: 438-441, 2003. [PubMed: 12660785] [Full Text: https://doi.org/10.1038/nature01506]

  209. Tang, M. X., Jacobs, D., Stern, Y., Marder, K., Schofield, P., Gurland, B., Andrews, H., Mayeux, R. Effect of oestrogen during menopause on risk and age of onset of Alzheimer's disease. Lancet 348: 429-432, 1996. [PubMed: 8709781] [Full Text: https://doi.org/10.1016/S0140-6736(96)03356-9]

  210. Tanzi, R. E., Bird, E. D., Latt, S. A., Neve, R. L. The amyloid beta protein gene is not duplicated in brains from patients with Alzheimer's disease. Science 238: 666-669, 1987. [PubMed: 2890207] [Full Text: https://doi.org/10.1126/science.2890207]

  211. Tanzi, R. E., Gusella, J. F., Watkins, P. C., Bruns, G. A. P., St. George-Hyslop, P., Van Keuren, M. L., Patterson, D., Pagan, S., Kurnit, D. M., Neve, R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235: 880-884, 1987. [PubMed: 2949367] [Full Text: https://doi.org/10.1126/science.2949367]

  212. Tanzi, R. E., McClatchey, A. I., Lamperti, E. D., Villa-Komaroff, L., Gusella, J. F., Neve, R. L. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature 331: 528-530, 1988. [PubMed: 2893290] [Full Text: https://doi.org/10.1038/331528a0]

  213. Tanzi, R. E., Vaula, G., Romano, D. M., Mortilla, M., Huang, T. L., Tupler, R. G., Wasco, W., Hyman, B. T., Haines, J. L., Jenkins, B. J., Kalaitsidaki, M., Warren, A. C., McInnis, M. C., Antonarakis, S. E., Karlinsky, H., Percy, M. E., Connor, L., Growdon, J., Crapper-McLachlan, D. R., Gusella, J. F., St. George-Hyslop, P. H. Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. Am. J. Hum. Genet. 51: 273-282, 1992. [PubMed: 1642228]

  214. Tanzi, R., St. George-Hyslop, P., Haines, J., Neve, R., Polinsky, R., Conneally, P. M., Gusella, J. F. Genetic linkage analysis of the Alzheimer's associated amyloid beta protein gene with familial Alzheimer's disease and chromosome 21. (Abstract) Cytogenet. Cell Genet. 46: 703 only, 1987.

  215. Taru, H., Kirino, Y., Suzuki, T. Differential roles of JIP scaffold proteins in the modulation of amyloid precursor protein metabolism. J. Biol. Chem. 277: 27567-27574, 2002. [PubMed: 12023290] [Full Text: https://doi.org/10.1074/jbc.M203713200]

  216. Tesseur, I., Zou, K., Esposito, L., Bard, F., Berber, E., Van Can, J., Lin, A. H., Crews, L., Tremblay, P., Mathews, P., Mucke, L., Masliah, E., Wyss-Coray, T. Deficiency in neuronal TGF-beta signaling promotes neurodegeneration and Alzheimer's pathology. J. Clin. Invest. 116: 3060-3069, 2006. [PubMed: 17080199] [Full Text: https://doi.org/10.1172/JCI27341]

  217. Theuns, J., Brouwers, N., Engelborghs, S., Sleegers, K., Bogaerts, V., Corsmit, E., De Pooter, T., van Duijn, C. M., De Deyn, P. P., Van Broeckhoven, C. Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer disease. Am. J. Hum. Genet. 78: 936-946, 2006. [PubMed: 16685645] [Full Text: https://doi.org/10.1086/504044]

  218. Tienari, P. J., Ida, N., Ikonen, E., Simons, M., Weidemann, A., Multhaup, G., Masters, C. L., Dotti, C. G., Beyreuther, K. Intracellular and secreted Alzheimer beta-amyloid species are generated by distinct mechanisms in cultured hippocampal neurons. Proc. Nat. Acad. Sci. 94: 4125-4130, 1997. [PubMed: 9108116] [Full Text: https://doi.org/10.1073/pnas.94.8.4125]

  219. Tong, Y., Xu, Y., Scearce-Levie, K., Ptacek, L. J., Fu, Y.-H. COL25A1 triggers and promotes Alzheimer's disease-like pathology in vivo. Neurogenetics 11: 41-52, 2010. [PubMed: 19548013] [Full Text: https://doi.org/10.1007/s10048-009-0201-5]

  220. Town, T., Laouar, Y., Pittenger, C., Mori, T., Szekely, C. A., Tan, J., Duman, R. S., Flavell, R. A. Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. (Letter) Nature Med. 14: 681-687, 2008. [PubMed: 18516051] [Full Text: https://doi.org/10.1038/nm1781]

  221. van Duijn, C. M., Hendriks, L., Cruts, M., Hardy, J. A., Hofman, A., Van Broeckhoven, C. Amyloid precursor protein gene mutation in early-onset Alzheimer's disease. (Letter) Lancet 337: 978 only, 1991. [PubMed: 1678057] [Full Text: https://doi.org/10.1016/0140-6736(91)91611-w]

  222. van Leeuwen, F. W., de Kleijn, D. P. V., van den Hurk, H. H., Neubauer, A., Sonnemans, M. A. F., Sluijs, J. A., Koycu, S., Ramdjielal, R. D. J., Salehi, A., Martens, G. J. M., Grosveld, F. G., Burbach, J. P. H., Hol, E. M. Frameshift mutants of beta-amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients. Science 279: 242-247, 1998. [PubMed: 9422699] [Full Text: https://doi.org/10.1126/science.279.5348.242]

  223. van Leeuwen, F. W., van Tijn, P., Sonnemans, M. A. F., Hobo, B., Mann, D. M. A., Van Broeckhoven, C., Kumar-Singh, S., Cras, P., Leuba, G., Savioz, A., Maat-Schieman, M. L. C., Yamaguchi, H., Kros, J. M., Kamphorst, W., Hol, E. M., de Vos, R. A. I., Fischer, D. F. Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies. Neurology 66 (suppl. 1): S86-S92, 2006. [PubMed: 16432153] [Full Text: https://doi.org/10.1212/01.wnl.0000193882.46003.6d]

  224. Van Nostrand, W. E., Wagner, S. L., Suzuki, M., Choi, B. H., Farrow, J. S., Geddes, J. W., Cotman, C. W., Cunningham, D. D. Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid beta-protein precursor. Nature 341: 546-549, 1989. [PubMed: 2507928] [Full Text: https://doi.org/10.1038/341546a0]

  225. Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Dents, P., Taplow, D. B., Ross, S., Amaranta, P., Loeloff, R., Luo, Y., Fisher, S., and 12 others. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286: 735-741, 1999. [PubMed: 10531052] [Full Text: https://doi.org/10.1126/science.286.5440.735]

  226. Walsh, D. M., Hartley, D. M., Condron, M. M., Selkoe, D. J., Teplow, D. B. In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692-to-Gly) Alzheimer's disease. Biochem. J. 355: 869-877, 2001. [PubMed: 11311152] [Full Text: https://doi.org/10.1042/bj3550869]

  227. Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., Selkoe, D. J. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535-539, 2002. [PubMed: 11932745] [Full Text: https://doi.org/10.1038/416535a]

  228. Warren, A. C., Robakis, N. K., Ramakrishna, N., Koo, E. H., Ross, C. A., Folstein, M. F., Price, D. L., Antonarakis, S. E. Beta-amyloid gene is not present in three copies in autopsy-validated Alzheimer's disease. Genomics 1: 307-312, 1987. [PubMed: 2966761] [Full Text: https://doi.org/10.1016/0888-7543(87)90029-2]

  229. Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., Kang, D. E., Marquez-Sterling, N., Golde, T. E., Koo, E. H. A subset of NSAIDs lower amyloidogenic A-beta-42 independently of cyclooxygenase activity. Nature 414: 212-216, 2001. [PubMed: 11700559] [Full Text: https://doi.org/10.1038/35102591]

  230. Willem, M., Tahirovic, S., Busche, M. A., Ovsepian, S. V., Chafai, M., Kootar, S., Hornburg, D., Evans, L. D. B., Moore, S., Daria, A., Hampel, H., Muller, V., and 15 others. Eta-secretase processing of APP inhibits neuronal activity in the hippocampus. Nature 526: 443-447, 2015. [PubMed: 26322584] [Full Text: https://doi.org/10.1038/nature14864]

  231. Wilson, C. A., Doms, R. W., Zheng, H., Lee, V. M.-Y. Presenilins are not required for A-beta-42 production in the early secretory pathway. Nature Neurosci. 5: 849-855, 2002. [PubMed: 12145638] [Full Text: https://doi.org/10.1038/nn898]

  232. Wyss-Coray, T., Lin, C., Yan, F., Yu, G., Rohde, M., McConlogue, L., Masliah, E., Mucke, L. TGF-beta-1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nature Med. 7: 612-618, 2001. [PubMed: 11329064] [Full Text: https://doi.org/10.1038/87945]

  233. Wyss-Coray, T., Masliah, E., Mallory, M., McConlogue, L., Johnson-Wood, K., Lin, C., Mucke, L. Amyloidogenic role of cytokine TGF-beta-1 in transgenic mice and in Alzheimer's disease. Nature 389: 603-606, 1997. [PubMed: 9335500] [Full Text: https://doi.org/10.1038/39321]

  234. Xu, H., Gouras, G. K., Greenfield, J. P., Vincent, B., Naslund, J., Mazzarelli, L., Fried, G., Jovanovic, J. N., Seeger, M., Relkin, N. R., Liao, F., Checler, F., Buxbaum, J. D., Chait, B. T., Thinakaran, G., Sisodia, S. S., Wang, R., Greengard, P., Gandy, S. Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nature Med. 4: 447-451, 1998. [PubMed: 9546791] [Full Text: https://doi.org/10.1038/nm0498-447]

  235. Yamatsuji, T., Matsui, T., Okamoto, T., Komatsuzaki, K., Takeda, S., Fukumoto, H., Iwatsubo, T., Suzuki, N., Asami-Odaka, A., Ireland, S., Kinane, T. B., Giambarella, U., Nishimoto, I. G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP. Science 272: 1349-1352, 1996. [PubMed: 8650548] [Full Text: https://doi.org/10.1126/science.272.5266.1349]

  236. Yan, R., Bienkowski, M. J., Shuck, M. E., Miao, H., Tory, M. C., Pauley, A. M., Brashler, J. R., Stratman, N. C., Mathews, W. R., Buhl, A. E., Carter, D. B., Tomasselli, A. G., Parodi, L. A., Heinrikson, R. L., Gurney, M. E. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature 402: 533-536, 1999. [PubMed: 10591213] [Full Text: https://doi.org/10.1038/990107]

  237. Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., Migheli, A., Nawroth, P., Stern, D., Schmidt, A. M. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 382: 685-691, 1996. [PubMed: 8751438] [Full Text: https://doi.org/10.1038/382685a0]

  238. Yoshikai, S., Sasaki, H., Doh-ura, K., Furuya, H., Sakaki, Y. Genomic organization of the human amyloid beta-protein precursor gene. Gene 87: 257-263, 1990. Note: Erratum: Gene 102: 291 only, 1991. [PubMed: 2110105] [Full Text: https://doi.org/10.1016/0378-1119(90)90310-n]

  239. Yoshioka, K., Miki, T., Katsuya, T., Ogihara, T., Sakaki, Y. The 717-val-to-ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups. Biochem. Biophys. Res. Commun. 178: 1141-1146, 1991. [PubMed: 1908231] [Full Text: https://doi.org/10.1016/0006-291x(91)91011-z]

  240. Yue, X., Lu, M., Lancaster, T., Cao, P., Honda, S.-I., Staufenbiel, M., Harada, N., Zhong, Z., Shen, Y., Li, R. Brain estrogen deficiency accelerates A-beta plaque formation in an Alzheimer's disease animal model. Proc. Nat. Acad. Sci. 102: 19198-19203, 2005. [PubMed: 16365303] [Full Text: https://doi.org/10.1073/pnas.0505203102]

  241. Zabel, B. U., Salbaum, J. M., Multhaup, G., Master, C. L., Bohl, J., Beyreuther, K. Sublocalization of the gene for the precursor of Alzheimer's disease amyloid A4 protein on chromosome 21. (Abstract) Cytogenet. Cell Genet. 46: 725-726, 1987.

  242. Zeldenrust, S. R., Murrell, J., Farlow, M., Ghetti, B., Roses, A. D., Benson, M. D. RFLP analysis for APP 717 mutations associated with Alzheimer's disease. J. Med. Genet. 30: 476-478, 1993. [PubMed: 7686976] [Full Text: https://doi.org/10.1136/jmg.30.6.476]

  243. Zhao, Y., Wang, Y., Hu, J., Zhang, X., Zhang, Y. CutA divalent cation tolerance homolog (Escherichia coli) (CUTA) regulates beta-cleavage of beta-amyloid precursor protein (APP) through interacting with beta-site APP cleaving protein 1 (BACE1). J. Biol. Chem. 287: 11141-11150, 2012. [PubMed: 22351782] [Full Text: https://doi.org/10.1074/jbc.M111.330209]

  244. Zhou, R., Yang, G., Guo, X., Zhou, Q., Lei, J., Shi, Y. Recognition of the amyloid precursor protein by human gamma-secretase. Science 363: eaaw0930, 2019. Note: Electronic Article. [PubMed: 30630874] [Full Text: https://doi.org/10.1126/science.aaw0930]

  245. Zhou, Y., Su, Y., Li, B., Liu, F., Ryder, J. W., Wu, X., Gonzalez-DeWhitt, P. A., Gelfanova, V., Hale, J. E., May, P. C., Paul, S. M., Ni, B. Nonsteroidal anti-inflammatory drugs can lower amyloidogenic A-beta(42) by inhibiting Rho. Science 302: 1215-1217, 2003. [PubMed: 14615541] [Full Text: https://doi.org/10.1126/science.1090154]

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