The Genetics of Alzheimer's Disease

The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics

Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864

Finding the missing heritability of complex diseases

Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336

Alzheimer's disease: the amyloid cascade hypothesis

Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

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

The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619

Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.

Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268

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

Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326

Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease

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

Candidate gene for the chromosome 1 familial Alzheimer’s disease locus

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., et al. (1995) · Science · doi:10.1126/science.7638622 · Cited by 2,577

Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene

Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., et al. (1995) · Nature · doi:10.1038/376775a0 · Cited by 2,052

The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease

Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022

Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease

Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

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

Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease

Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., & Hirschhorn, J. N. (2003) · Nature Genetics · doi:10.1038/ng1071 · Cited by 1,900

Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database

Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857

Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein

De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., & Van Leuven, F. (1998) · Nature · doi:10.1038/34910 · Cited by 1,818

Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer Locus

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. (1987) · Science · doi:10.1126/science.2949367 · Cited by 1,611

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

Soscia, S. J., Kirby, J. E., Washicosky, K. J., Tucker, S. M., Ingelsson, M., Hyman, B., Burton, M. A., Goldstein, L. E., Duong, S., Tanzi, R. E., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009505 · Cited by 1,060

Rare Variants of IFIH1 , a Gene Implicated in Antiviral Responses, Protect Against Type 1 Diabetes

Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958

Rare Variants Create Synthetic Genome-Wide Associations

Dickson, S. P., Wang, K., Krantz, I., Hakonarson, H., & Goldstein, D. B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000294 · Cited by 857

Whole-Genome Sequencing in a Patient with Charcot–Marie–Tooth Neuropathy

Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0908094 · Cited by 759

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

The genetic epidemiology of neurodegenerative disease

Bertram, L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24761 · Cited by 680

A High-Density Whole-Genome Association Study Reveals That APOE Is the Major Susceptibility Gene for Sporadic Late-Onset Alzheimer's Disease

Coon, K. D., Myers, A. J., Craig, D. W., Webster, J. A., Pearson, J. V., Lince, D. H., Zismann, V. L., Beach, T. G., Leung, D., Bryden, L., et al. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n0419 · Cited by 569

γ-Secretase, notch, Aβ and alzheimer's disease: Where do the presenilins fit in?

Sisodia, S. S., & St George-Hyslop, P. H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn785 · Cited by 512

Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations

Bilgüvar, K., Öztürk, A. K., Louvi, A., Kwan, K. Y., Choi, M., Tatlı, B., Yalnızoğlu, D., Tüysüz, B., Çağlayan, A. O., Gökben, S., et al. (2010) · Nature · doi:10.1038/nature09327 · Cited by 503

Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease

Li, H., Wetten, S., Li, L., St. Jean, P. L., Upmanyu, R., Surh, L., Hosford, D., Barnes, M. R., Briley, J. D., Borrie, M., et al. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.3 · Cited by 499

ApoE and Clusterin Cooperatively Suppress Aβ Levels and Deposition

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., et al. (2004) · Neuron · doi:10.1016/s0896-6273(03)00850-x · Cited by 459

Incidence and Risk of Dementia: The Rotterdam study

Ott, A., Breteler, M. M. B., Harskamp, F. V., Stijnen, T., & Hofman, A. (1998) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009489 · Cited by 455

Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy

Nicot, A.-S., Toussaint, A., Tosch, V., Kretz, C., Wallgren-Pettersson, C., Iwarsson, E., Kingston, H., Garnier, J.-M., Biancalana, V., Oldfors, A., et al. (2007) · Nature Genetics · doi:10.1038/ng2086 · Cited by 434

Relation of Plasma Lipids to Alzheimer Disease and Vascular Dementia

Reitz, C., Tang, M.-X., Luchsinger, J., & Mayeux, R. (2004) · Archives of Neurology · doi:10.1001/archneur.61.5.705 · Cited by 397

Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease

Potkin, S. G., Guffanti, G., Lakatos, A., Turner, J. A., Kruggel, F., Fallon, J. H., Saykin, A. J., Orro, A., Lupoli, S., Salvi, E., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006501 · Cited by 376

Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance

Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274

Proteins of the CNR Family Are Multiple Receptors for Reelin

Senzaki, K., Ogawa, M., & Yagi, T. (1999) · Cell · doi:10.1016/s0092-8674(00)81552-4 · Cited by 272

Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease

Kehoe, P. G., Russ, C., McIlroy, S., Williams, H., Holmans, P., Holmes, C., Liolitsa, D., Vahidassr, D., Powell, J., McGleenon, B., et al. (1999) · Nature Genetics · doi:10.1038/5009 · Cited by 260

Genome-wide Association Study Implicates a Chromosome 12 Risk Locus for Late-Onset Alzheimer Disease

Beecham, G. W., Martin, E. R., Li, Y.-J., Slifer, M. A., Gilbert, J. R., Haines, J. L., & Pericak-Vance, M. A. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.12.008 · Cited by 260

Molecular Dissection of the Interaction between Amyloid Precursor Protein and Its Neuronal Trafficking Receptor SorLA/LR11

Andersen, O. M., Schmidt, V., Spoelgen, R., Gliemann, J., Behlke, J., Galatis, D., McKinstry, W. J., Parker, M. W., Masters, C. L., Hyman, B. T., et al. (2006) · Biochemistry · doi:10.1021/bi052120v · Cited by 178

Peripheral clearance of amyloid β peptide by complement C3-dependent adherence to erythrocytes

Rogers, J., Li, R., Mastroeni, D., Grover, A., Leonard, B., Ahern, G., Cao, P., Kolody, H., Vedders, L., Kolb, W. P., et al. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.043 · Cited by 175

Apolipoprotein E and β-amyloid levels in the hippocampus and frontal cortex of Alzheimer's disease subjects are disease-related and apolipoprotein E genotype dependent

Beffert, U., Cohn, J. S., Petit-Turcotte, C., Tremblay, M., Aumont, N., Ramassamy, C., Davignon, J., & Poirier, J. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01894-6 · Cited by 142

Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis

Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124

Distribution and Expression of Picalm in Alzheimer Disease

Baig, S., Joseph, S. A., Tayler, H., Abraham, R., Owen, M. J., Williams, J., Kehoe, P. G., & Love, S. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181f52e01 · Cited by 115

LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease

Abisambra, J. F., Fiorelli, T., Padmanabhan, J., Neame, P., Wefes, I., & Potter, H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008556 · Cited by 42

Super-enhancers in the control of cell identity and disease

Hnisz, D., Abraham, B. J., Lee, T. I., Lau, A., Saint-André, V., Sigova, A. A., Hoke, H. A., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.09.053 · Cited by 3,662

Microglia Function in the Central Nervous System During Health and Neurodegeneration

Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894

Blood-Brain Barrier: From Physiology to Disease and Back

Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312

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

Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria

Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.02.002 · Cited by 1,925