Candidate gene for the chromosome 1 familial Alzheimer’s disease locus
Abstract
A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141l), was identified in affected people from Volga German AD kindreds. This N141l mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic.
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Cites
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · see citing works
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · see citing works
Self-citationChartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., et al. (1991) · Nature · doi:10.1038/353844a0 · Cited by 1,214 · see citing works
A mutation in the Amyloid Precursor Protein Associated with Hereditary Alzheimer's Disease
Murrell, J. R., Farlow, M. R., Ghetti, B. F., & Benson, M. D. (1991) · Science · doi:10.1126/science.1925564 · Cited by 1,122 · see citing works
Genetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Orr, H. T., Anderson, L., Nemens, E. J., White, J. A., Bonnycastle, L. L., Weber, J. L., Alonso, M. E., et al. (1992) · Science · doi:10.1126/science.1411576 · Cited by 945 · see citing works
Self-citationA Familial Alzheimer's Disease Locus on Chromosome 1
Levy‐Lahad, E., Wijsman, E. M., Nemens, E. J., Anderson, L., Goddard, K. A. B., Weber, J. L., Bird, T. D., & Schellenberg, G. D. (1995) · Science · doi:10.1126/science.7638621 · Cited by 812 · see citing works
Self-citationEffects of Misspecifying Genetic Parameters in Lod Score Analysis
Clerget‐Darpoux, F., Bonaïti‐Pellié, C., & Hochez, J. (1986) · Biometrics · doi:10.2307/2531059 · Cited by 439 · see citing works
Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region.
Kamino, K., Orr, H. T., Payami, H., Wijsman, E. M., Alonso, M. E., Pulst, S. M., Anderson, L., O'dahl, S., Nemens, E. J., & White, J. A. (1992) · PubMed · Cited by 268 · see citing works
Self-citationMullan, M., Houlden, H., Windelspecht, M., Fidani, L., Lombardi, C., Diaz, P., Rossor, M. N., Crook, R., Hardy, J., Duff, K., et al. (1992) · Nature Genetics · doi:10.1038/ng1292-340 · Cited by 267 · see citing works
Absence of Linkage of Chromosome 21q21 Markers to Familial Alzheimer's Disease
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Moore, D. K., Boehnke, M., Bryant, E. M., Lampe, T. H., Nochlin, D., Sumi, S. M., Deeb, S. S., et al. (1988) · Science · doi:10.1126/science.3420406 · Cited by 242 · see citing works
Self-citationPhenotypic heterogeneity in familial alzheimer's disease: A study of 24 kindreds
Bird, T. D., Sumi, S. M., Nemens, E. J., Nochlin, D., Schellenberg, G. D., Lampe, T. H., Sadovnick, A. D., Chui, H. C., Miner, G. W., & Tinklenberg, J. R. (1989) · Annals of Neurology · doi:10.1002/ana.410250104 · Cited by 168 · see citing works
Self-citationL’Hernault, S. W., & Arduengo, P. M. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.119.1.55 · Cited by 158 · see citing works
Bird, T. D., Lampe, T. H., Nemens, E. J., Miner, G. W., Sumi, S. M., & Schellenberg, G. D. (1988) · Annals of Neurology · doi:10.1002/ana.410230106 · Cited by 147 · see citing works
Self-citationCook-Deegan, R. M., Ward, B. E., & Austin, J. H. (1979) · Neurology · doi:10.1212/wnl.29.10.1402 · Cited by 117 · see citing works
Heterogeneity of Alzheimer’s Disease
(1992) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-46776-9 · Cited by 93 · see citing works
APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease.
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. (1991) · PubMed · Cited by 87 · see citing works
Self-citationNakanishi, H., Tsukuba, T., 近藤照義, Tanaka, T., & Yamamoto, K. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1088 · Cited by 68 · see citing works
Linkage analysis of familial Alzheimer disease, using chromosome 21 markers.
Schellenberg, G. D., Pericak‐Vance, M. A., Wijsman, E. M., Moore, D. K., Gaskell, P. C., Yamaoka, L. A., Bebout, J., Anderson, L., Welsh-Bohmer, K. A., & Clark, C. M. (1991) · PubMed · Cited by 67 · see citing works
Self-citationChromosome 14 and late-onset familial Alzheimer disease (FAD).
Schellenberg, G. D., Payami, H., Wijsman, E. M., Orr, H. T., Goddard, K. A. B., Anderson, L., Nemens, E. J., White, J. A., Alonso, M. E., & Ball, M. J. (1993) · PubMed · Cited by 58 · see citing works
Self-citationLinkage of familial breast cancer to chromosome 17q21 may not be restricted to early-onset disease.
Margaritte‐Jeannin, P., Bonaïti‐Pellié, C., King, M., & Clerget‐Darpoux, F. (1992) · Europe PMC (PubMed Central) · Cited by 52 · see citing works
Systematic screening of an arrayed cDNA library by PCR.
Munroe, D. J., Loebbert, R. W., Bric, E., Whitton, T., Prawitt, D., Vu, D. M., Buckler, A., Winterpacht, A., Zabel, B., & Housman, D. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.6.2209 · Cited by 48 · see citing works
An immunohistochemical study of cathepsin E in Alzheimer-type dementia brains
Bernstein, H., & Wiederanders, B. (1994) · Brain Research · doi:10.1016/0006-8993(94)91509-1 · Cited by 43 · see citing works
Azuma, T., Liu, W., der Laan, D. J. V., Bowcock, A. M., & Taggart, R. T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45989-3 · Cited by 37 · see citing works
Bergquist, J. M., Scheuerman, R. D., & Trafzer, C. E. (1981) · The American Historical Review · doi:10.1086/ahr/86.5.1162 · Cited by 10 · see citing works
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Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Gauthier, S. G., Reisberg, ., Zaudig, M., Petersen, R. C., Ritchie, K. A., Broich, K., Belleville, S., Brodaty, H., Bennett, D. A., Chertkow, H. M., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68542-5 · Cited by 3,920 · see citing works
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134 · see citing works
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · see citing works
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Self-citationOxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383 · see citing works
Ballard, C., Gauthier, S., Corbett, A., Brayne, C., Aarsland, D., & Jones, E. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61349-9 · Cited by 2,336 · see citing works
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188 · see citing works
A Century of Alzheimer's Disease
Goedert, M., & Spillantini, M. G. (2006) · Science · doi:10.1126/science.1132814 · Cited by 2,106 · see citing works
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Self-citationApoptosis in the nervous system
Yuan, J., & Yankner, B. A. (2000) · Nature · doi:10.1038/35037739 · Cited by 1,862 · see citing works
Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
Tanzi, R. E., & Bertram, L. (2005) · Cell · doi:10.1016/j.cell.2005.02.008 · Cited by 1,849 · see citing works
Self-citationGaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006) · Chemical Reviews · doi:10.1021/cr040410w · Cited by 1,729 · see citing works
Defeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Translating cell biology into therapeutic advances in Alzheimer's disease
Selkoe, D. J. (1999) · Nature · doi:10.1038/399a023 · Cited by 1,588 · see citing works
Memory and Executive Function in Aging and AD
Buckner, R. L. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.006 · Cited by 1,508 · see citing works
Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80230-5 · Cited by 1,478 · see citing works
Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,453 · see citing works
Alzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424 · see citing works
Brookes, A. J. (1999) · Gene · doi:10.1016/s0378-1119(99)00219-x · Cited by 1,381 · see citing works
Tau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374 · see citing works
Self-citationAmyloid, the presenilins and Alzheimer’s disease
Hardy, J. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01030-2 · Cited by 1,370 · see citing works
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · see citing works
Toxic Proteins in Neurodegenerative Disease
Taylor, J. P., Hardy, J., & Fischbeck, K. H. (2002) · Science · doi:10.1126/science.1067122 · Cited by 1,251 · see citing works
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Lomakin, A., Benedek, G. B., Condron, M. M., & Teplow, D. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.22364 · Cited by 1,139 · see citing works
Epidemiology of Alzheimer DiseasePreprint
Mayeux, R. P., & Stern, Y. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006239 · Cited by 1,070 · see citing works
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Hartley, D. M., Kusumoto, Y., Fezoui, Y., Condron, M. M., Lomakin, A., Benedek, G. B., Selkoe, D. J., & Teplow, D. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25945 · Cited by 1,046 · see citing works
Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Endoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives In Vivo
Thinakaran, G., Borchelt, D., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G. J., Ratovitski, T., Davenport, F., Nordstedt, C., Seeger, M., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80291-3 · Cited by 1,009 · see citing works
Role of Glutamate and NMDA Receptors in Alzheimer’s Disease
Wang, R., & Reddy, P. H. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160763 · Cited by 1,009 · see citing works
Biomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002 · see citing works
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · see citing works
Diagnosis and Treatment of Alzheimer Disease and Related Disorders
Small, G. W. (1997) · JAMA · doi:10.1001/jama.1997.03550160083043 · Cited by 984 · see citing works
APP processing in Alzheimer’s disease.
Zhang, Y.-W., Thompson, R., Zhang, H., & Xu, H. (2011) · Molecular Brain · doi:10.1186/1756-6606-4-3 · Cited by 983 · see citing works
Goedert, M. (2015) · Science · doi:10.1126/science.1255555 · Cited by 977 · see citing works
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 947 · see citing works
Alzheimer's Disease--Genotypes, Phenotype, and Treatments
Selkoe, D. J. (1997) · Science · doi:10.1126/science.275.5300.630 · Cited by 871 · see citing works
The genetic landscape of Alzheimer disease: clinical implications and perspectives
Van Cauwenberghe, C., Van Broeckhoven, C., & Sleegers, K. (2016) · Genetics in Medicine · doi:10.1038/gim.2015.117 · Cited by 863 · see citing works
Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases
Selkoe, D. J. (2004) · Nature Cell Biology · doi:10.1038/ncb1104-1054 · Cited by 863 · see citing works
The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease
Selkoe, D. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01363-4 · Cited by 862 · see citing works
The amyloid hypothesis for Alzheimer’s disease: A critical reappraisal
Hardy, J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06181.x · Cited by 814 · see citing works
Pharmacogenetics and the practice of medicine
Roses, A. D. (2000) · Nature · doi:10.1038/35015728 · Cited by 803 · see citing works
Amyloid β-Protein and the Genetics of Alzheimer's Disease
Selkoe, D. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.31.18295 · Cited by 798 · see citing works
GSK3 inhibitors: development and therapeutic potential
Cohen, P., & Goedert, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1415 · Cited by 788 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
“In other families, FAD linkage studies helped identify mutations in two related genes, PSEN1 and PSEN2 [11, 12].”
BackgroundThe Genetics of Alzheimer's Disease
Bertram, L., & Tanzi, R. E. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00008-4 · Cited by 784 · see citing works
Self-citationA “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · see citing works
Turner, P. R., O’Connor, K., Tate, W. P., & Abraham, W. C. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00089-3 · Cited by 751 · see citing works
Protein aggregation diseases: pathogenicity and therapeutic perspectives
Aguzzi, A., & O’Connor, T. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3050 · Cited by 750 · see citing works
Autophagy, amyloidogenesis and Alzheimer disease
Nixon, R. A. (2007) · Journal of Cell Science · doi:10.1242/jcs.019265 · Cited by 749 · see citing works
Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747 · see citing works
Self-citationTREM2 — a key player in microglial biology and Alzheimer disease
Ulland, T. K., & Colonna, M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0072-1 · Cited by 735 · see citing works
The genetics of Alzheimer disease
Tanzi, R. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006296 · Cited by 727 · see citing works
Self-citationNeurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
Forman, M. S., Trojanowski, J. Q., & Lee, V. M.-Y. (2004) · Nature Medicine · doi:10.1038/nm1113 · Cited by 715 · see citing works
Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesoderm
Wong, P. C., Zheng, H., Chen, H., Bêcher, M. W., SIRINATHSINGHJI, D. J. S., Trumbauer, M. E., Chen, H. Y., Price, D. L., der Ploeg, L. H. T. V., & Sisodia, S. S. (1997) · Nature · doi:10.1038/387288a0 · Cited by 712 · see citing works
APOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE
Roses, M. D. (1996) · Annual Review of Medicine · doi:10.1146/annurev.med.47.1.387 · Cited by 707 · see citing works
Šimić, G., Leko, M. B., Wray, S., Harrington, C. R., Delalle, I., Milošević, N. J., Bažadona, D., Buée, L., de Silva, R., Giovanni, G. D., et al. (2016) · Biomolecules · doi:10.3390/biom6010006 · Cited by 698 · see citing works
The genetic epidemiology of neurodegenerative disease
Bertram, L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24761 · Cited by 680 · see citing works
Yankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · see citing works
The Amyloid Precursor Protein of Alzheimer's Disease in the Reduction of Copper(II) to Copper(I)
Multhaup, G., Schlicksupp, A., Hesse, L., Beher, D., Ruppert, T., Masters, C. L., & Beyreuther, K. T. (1996) · Science · doi:10.1126/science.271.5254.1406 · Cited by 677 · see citing works
Hardeland, R. (2005) · Endocrine · doi:10.1385/endo:27:2:119 · Cited by 670 · see citing works
N OTCH AND P RESENILIN : Regulated Intramembrane Proteolysis Links Development and Degeneration
Selkoe, D. J., & Kopan, R. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131334 · Cited by 630 · see citing works
Proteolytic processing and cell biological functions of the amyloid precursor protein
Strooper, B. D., & Annaert, W. G. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.11.1857 · Cited by 628 · see citing works
Molecular genetics of early-onset Alzheimer’s disease revisited
Cacace, R., Sleegers, K., & Van Broeckhoven, C. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.012 · Cited by 617 · see citing works
Risk factors for Alzheimer’s disease
Armstrong, R. A. (2019) · Folia Neuropathologica · doi:10.5114/fn.2019.85929 · Cited by 617 · see citing works
Modeling familial Alzheimer's disease with induced pluripotent stem cells
Yagi, T., Ito, D., Okada, Y., Akamatsu, W., Nihei, Y., Yoshizaki, T., Yamanaka, S., Okano, H., & Suzuki, N. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr394 · Cited by 599 · see citing works
Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease
Barage, S. H., & Sonawane, K. D. (2015) · Neuropeptides · doi:10.1016/j.npep.2015.06.008 · Cited by 579 · see citing works
Raja, W. K., Mungenast, A. E., Lin, Y.-T., Ko, T., Abdurrob, F., Seo, J., & Tsai, L.-H. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161969 · Cited by 569 · see citing works
MUTANT GENES IN FAMILIAL ALZHEIMER'S DISEASE AND TRANSGENIC MODELS
Price, D. L., & Sisodia, S. S. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.479 · Cited by 568 · see citing works
The road to restoring neural circuits for the treatment of Alzheimer's disease
Canter, R. G., Penney, J., & Tsai, L.-H. (2016) · Nature · doi:10.1038/nature20412 · Cited by 565 · see citing works
Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk
Efthymiou, A. G., & Goate, A. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0184-x · Cited by 562 · see citing works
The Alzheimer’s Disease Mitochondrial Cascade Hypothesis
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100339 · Cited by 562 · see citing works
The Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550 · see citing works
Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines.
Wischik, C. M., Edwards, P. C., Lai, R. Y., Roth, M., & Harrington, C. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.11213 · Cited by 547 · see citing works
Linking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis
Small, S. A., & Duff, K. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.007 · Cited by 546 · see citing works
Zinc Metabolism in the Brain: Relevance to Human Neurodegenerative Disorders
Cuajungco, M. P., & Lees, G. J. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0163 · Cited by 540 · see citing works
Inhibition of Heparin-induced Tau Filament Formation by Phenothiazines, Polyphenols, and Porphyrins
Taniguchi, S., Suzuki, N., Masuda, M., Hisanaga, S., Iwatsubo, T., Goedert, M., & Hasegawa, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408714200 · Cited by 540 · see citing works
Lee, W., Loo, C., Bebawy, M., Luk, F., Mason, R. S., & Rohanizadeh, R. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311040002 · Cited by 539 · see citing works
Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease
Morris, G. P., Clark, I. A., & Vissel, B. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0135-5 · Cited by 522 · see citing works
Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response
Katayama, T., Imaizumi, K., Sato, N., Miyoshi, K., Kudo, T., Hitomi, J., Morihara, T., Yoneda, T., Gomi, F., Mori, Y., et al. (1999) · Nature Cell Biology · doi:10.1038/70265 · Cited by 521 · see citing works
Hsiao, K., Borchelt, D., Olson, K., Johannsdottir, R., Kitt, C. A., Yunis, W. S., Xu, S., Eckman, C., Younkin, S. G., Price, D., et al. (1995) · Neuron · doi:10.1016/0896-6273(95)90107-8 · Cited by 519 · see citing works
Herreman, A., Hartmann, D., Annaert, W. G., Säftig, P., Craessaerts, K., Serneels, L., Umans, L., Schrijvers, V., Checler, F., Vanderstichele, H., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.11872 · Cited by 518 · see citing works
Molecular Targets of Lithium Action
Phiel, C. J., & Klein, P. S. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.789 · Cited by 513 · see citing works
Bertram, L., Lange, C., Mullin, K., Parkinson, M., Hsiao, M., Hogan, M. F., Schjeide, B. M. M., Hooli, B., DiVito, J., Ionita, I., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.10.008 · Cited by 511 · see citing works
Self-citationDestabilization of β-catenin by mutations in presenilin-1 potentiates neuronal apoptosis
Zhang, Z., Hartmann, H., Do, V. M., Abramowski, D., Sturchler, C., Staufenbiel, M., Sommer, B., van de Wetering, M., Clevers, H. C., Säftig, P., et al. (1998) · Nature · doi:10.1038/27208 · Cited by 511 · see citing works
A Portrait of Alzheimer Secretases--New Features and Familiar Faces
Esler, W. P., & Wolfe, M. S. (2001) · Science · doi:10.1126/science.1064638 · Cited by 493 · see citing works
The Many Substrates of Presenilin/γ-Secretase
Haapasalo, A., & Kovacs, D. M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101065 · Cited by 487 · see citing works
Guo, Q., Sopher, B. L., Furukawa, K., Pham, D. G., Robinson, N., Martin, G. M., & Mattson, M. P. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-11-04212.1997 · Cited by 487 · see citing works
Clark, R. F., Hutton, M., Fuldner, M., Froelich, S., Karran, E., Talbot, C., Crook, R., Lendon, C., Prihar, G., He, C., et al. (1995) · Nature Genetics · doi:10.1038/ng1095-219 · Cited by 474 · see citing works
Modeling Alzheimer’s disease with iPSC-derived brain cells
Penney, J., Ralvenius, W. T., & Tsai, L.-H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0468-3 · Cited by 471 · see citing works
Interfering with Apoptosis: Ca 2+ -Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3
Vito, P., Lacaná, E., & D'adamio, L. (1996) · Science · doi:10.1126/science.271.5248.521 · Cited by 468 · see citing works
The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy
McGeer, P. L., & McGeer, E. G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1177-7 · Cited by 467 · see citing works
Suh, Y.-H., & Checler, F. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.3.469 · Cited by 467 · see citing works
A Hundred Years of Alzheimer's Disease Research
Hardy, J. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.016 · Cited by 467 · see citing works
Presenilins and -Secretase: Structure, Function, and Role in Alzheimer DiseasePreprint
Strooper, B. D., Iwatsubo, T., & Wolfe, M. S. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006304 · Cited by 465 · see citing works
Mice lacking both presenilin genes exhibitearlyembryonic patterningdefectsPreprint
Donoviel, D. B., Hadjantonakis, A., Ikeda, M., Zheng, H., George‐Hyslop, P. S., & Bernstein, A. (1999) · Genes & Development · doi:10.1101/gad.13.21.2801 · Cited by 457 · see citing works
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
De Strooper, B. (2010) · Physiological Reviews · doi:10.1152/physrev.00023.2009 · Cited by 455 · see citing works
- Authors
- Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C.-E., Jondro, P. D., Schmidt, S. D., Wang, K., Crowley, A. C., Fu, Y.-H., Guenette, S. Y., Galas, D., Nemens, E., Wijsman, E. M., Bird, T. D., Schellenberg, G. D., & Tanzi, R. E.
- Affiliations
- Geriatric Research Education, and Clinical Center (182B), Veterans Affairs Medical Center, Seattle, WA 98108, USA.
- Massachusetts General Hospital (US)
- United States Department of Veterans Affairs (US)
- Darwin Molecular, Bothell, WA 98021, USA.
- Genetics and Aging Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
- University of Washington (US)
- ORCID
- Venue
- Science
- Published
- 1995-08-18
- Volume
- 269
- Issue
- 5226
- Pages
- 973-977
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2083633251
- Cited by
- 2,577
- References
- 25
- Citations by year
- 2026: 17 · 2025: 46 · 2024: 66 · 2023: 47 · 2022: 43 · 2021: 65 · 2020: 84 · 2019: 72 · 2018: 65 · 2017: 77 · 2016: 90 · 2015: 63 · 2014: 78 · 2013: 82 · 2012: 83
- FWCI
- 99.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag011899-03)
- National Institute on Aging (AG0513C, R01AG011762, R01 AG 11762, R01-AG11899)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- familial Alzheimer's disease, candidate genes, missense mutations, gene homology, pathogenic variants
- MeSH terms
- Adult, Aged, Alzheimer Disease, Amino Acid Sequence, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 1, Cloning, Molecular, Female, Germany, Humans, Lod Score, Male, Membrane Proteins, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Gene Expression, Point Mutation, DNA, Complementary, Presenilin-2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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