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Autosomal Recessive Causes Likely in Early-Onset Alzheimer Disease
Open accessAbstract
OBJECTIVES: To determine the genetic contribution to non-autosomal dominant early-onset Alzheimer disease (EOAD) (onset age ≤60 years) cases and identify the likely mechanism of inheritance in those cases. DESIGN: A liability threshold model of disease was used to estimate heritability of EOAD and late-onset Alzheimer disease (AD) using concordance for AD among parent-offspring pairs. SETTING: The Uniform Data Set, whose participants were collected from 32 US Alzheimer's Disease Centers, maintained by the National Alzheimer's Coordinating Center. PARTICIPANTS: Individuals with probable AD and detailed parental history (n = 5370). MAIN OUTCOME MEASURES: The concordance among relatives and heritability of EOAD and late-onset AD. RESULTS: For late-onset AD (n = 4302), we found sex-specific parent-offspring concordance that ranged from approximately 10% to 30%, resulting in a heritability of 69.8% (95% confidence interval, 64.6%-75.0%), and equal heritability for both sexes regardless of parental sex. For EOAD (n = 702), we found that the parent-offspring concordance was 10% or less and concordance among siblings was 21.6%. Early-onset AD heritability was 92% to 100% for all likely values of EOAD prevalence. CONCLUSIONS: We confirm late-onset AD is a highly polygenic disease. By contrast, the data for EOAD suggest it is an almost entirely genetically based disease, and the patterns of observed concordance for parent-offspring pairs and among siblings lead us to reject the hypotheses that EOAD is a purely dominant, mitochondrial, X-linked, or polygenic disorder. The most likely explanation of the data is that approximately 90% of EOAD cases are due to autosomal recessive causes.
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“Estimates of heritability for EOAD are as high as 90–100% [24]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [24]
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“it has been estimated that up to 90% of EOAD may be caused by recessive mutations [24]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [24]
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Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. L., & Stadlan, E. (2011) · Neurology · doi:10.1212/01.wnl.0000400650.92875.cf · Cited by 9,882
Alzheimer Disease in the US Population: Prevalence Estimates Using the 2000 Census
Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D. A., & Evans, D. A. (2003) · Archives of Neurology · doi:10.1001/archneur.60.8.1119 · Cited by 2,168
Mixed brain pathologies account for most dementia cases in community-dwelling older persons
Schneider, J. A., Arvanitakis, Z., Bang, W., & Bennett, D. A. (2007) · Neurology · doi:10.1212/01.wnl.0000271090.28148.24 · Cited by 1,992
Exome sequencing identifies the cause of a mendelian disorder
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., Huff, C. D., Shannon, P. T., Jabs, E. W., Nickerson, D. A., et al. (2010) · Nature Genetics · doi:10.1038/ng.499 · Cited by 1,957
Role of Genes and Environments for Explaining Alzheimer Disease
Gatz, M., Reynolds, C. A., Fratiglioni, L., Johansson, B., Mortimer, J. A., Berg, S., Fiske, A., & Pedersen, N. L. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.2.168 · Cited by 1,798
The inheritance of liability to certain diseases, estimated from the incidence among relatives
Falconer, D. (1965) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1965.tb00500.x · Cited by 1,662
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627
Alzheimer's Disease and Parkinson's Disease
Nussbaum, R. L., & Ellis, C. E. (2003) · New England Journal of Medicine · doi:10.1056/nejm2003ra020003 · Cited by 1,351
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219
Morris, J. C., Weintraub, S., Chui, H. C., Cummings, J., DeCarli, C., Ferris, S., Foster, N. L., Galasko, D., Graff-Radford, N., Peskind, E. R., et al. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213865.09806.92 · Cited by 950
The Alzheimer's Disease Centers' Uniform Data Set (UDS)
Weıntraub, S., Salmon, D. P., Mercaldo, N. D., Ferris, S. H., Graff‐Radford, N. R., Chui, H. C., Cummings, J. L., DeCarli, C. S., Foster, N. L., Galasko, D. R., et al. (2009) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318191c7dd · Cited by 911
The National Alzheimer's Coordinating Center (NACC) Database: The Uniform Data Set
Beekly, D. L., Ramos, E. M., Lee, W. W., Deitrich, W. D., Jacka, M. E., Wu, J., Hubbard, J. L., Koepsell, T. D., Morris, J. C., & Kukull, W. A. (2007) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318142774e · Cited by 907
Campion, D., Dumanchin, C., Hannequin, D., Dubois, B., Belliard, S., Puel, M., Thomas-Anterion, C., Michon, A., Martin, C., Charbonnier, F., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302553 · Cited by 785
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
The prevalence and causes of dementia in people under the age of 65 years
Harvey, R. J. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.9.1206 · Cited by 650
Evans, D. A., Funkenstein, H. H., Albert, M., Scherr, P. A., Cook, N. R., Chown, M. J., Hebert, L. E., Hennekens, C. H., & Taylor, J. O. (1989) · PubMed · Cited by 599
The diagnosis of young-onset dementia
Rossor, M. N., Fox, N. C., Mummery, C. J., Schott, J. M., & Warren, J. D. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70159-9 · Cited by 585
Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study
Bachman, D. L., Wolf, P. A., Linn, R., Knoefel, J. E., CobbS, J., Belanger, A., D'Agostino, R. B., & White, L. R. (1992) · Neurology · doi:10.1212/wnl.42.1.115 · Cited by 527
Apolipoprotein E4 allele in a population–based study of early–onset Alzheimer's disease
van Duijn, C. M., de Knijff, P., Cruts, M., Wehnert, A., Havekes, L. M., Albert Hofman, D., & Broeckhoven, C. V. (1994) · Nature Genetics · doi:10.1038/ng0594-74 · Cited by 459
Incidence and Prevalence of Dementia in the Cardiovascular Health Study
Fitzpatrick, A. L., Kuller, L. H., Ives, D. G., Lopez, O. L., Jagust, W., Breitner, J. C. S., Jones, B., Lyketsos, C., & Dulberg, C. (2004) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2004.52058.x · Cited by 438
A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis
Fede, G. D., Catania, M., Morbin, M., Rossi, G., Suardi, S., Mazzoleni, G., Merlin, M., Gıovagnolı, A. R., Prioni, S., Erbetta, A., et al. (2009) · Science · doi:10.1126/science.1168979 · Cited by 429
APOE -ε4 count predicts age when prevalence of AD increases, then declines: The Cache County Study
Breitner, J. C. S., Wyse, B. W., Anthony, J. C., Welsh-Bohmer, K. A., Steffens, D. C., Norton, M. C., Tschanz, J. T., Plassman, B. L., Meyer, M. R., Skoog, I., et al. (1999) · Neurology · doi:10.1212/wnl.53.2.321 · Cited by 397
Evans, D. A., Bennett, D. A., Wilson, R. S., Bienias, J. L., Morris, M. C., Scherr, P. A., Hebert, L. E., Aggarwal, N., Beckett, L. A., Joglekar, R., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.2.185 · Cited by 370
The Number of Trait Loci in Late-Onset Alzheimer Disease
Daw, E. W., Payami, H., Nemens, E. J., Nochlin, D., Bird, T. D., Schellenberg, G. D., & Wijsman, E. M. (2000) · The American Journal of Human Genetics · doi:10.1086/302710 · Cited by 295
Bates, K. A., Verdile, G., Li, Q.-X., Ames, D., Hudson, P., Masters, C. L., & Martins, R. N. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.96 · Cited by 247
The Role of Heredity in Late-Onset Alzheimer Disease and Vascular Dementia
Bergem, A. L. M. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830150090013 · Cited by 208
Breitner, J. C. S. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540320035011 · Cited by 178
The Prevalence and 3-Year Incidence of Dementia in Older Black and White Community Residents
Fillenbaum, G. G., Heyman, A., Huber, M., Woodbury, M. A., Leiss, J. K., Schmader, K. E., Bohannon, A., & Trapp-Moen, B. (1998) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(98)00024-9 · Cited by 163
Transmission and age‐at‐onset patterns in familial Alzheimer's disease
Farrer, L. A., Myers, R. H., Cupples, L. A., George‐Hyslop, P. S., Bird, T. D., Rossor, M. N., MULLAN, M. J., Polinsky, R. J., Nee, L. E., Heston, L. L., et al. (1990) · Neurology · doi:10.1212/wnl.40.3_part_1.395 · Cited by 125
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124
Alzheimer's disease in Finnish twins
Räihä, I. J., Rajala, T., Sourander, L., Kaprio, J. A., & Koskenvuo, M. (1996) · The Lancet · doi:10.1016/s0140-6736(96)91272-6 · Cited by 123
An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease
Roses, A. D. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.88 · Cited by 118
Newens, A. J., Forster, D. P., Kay, D. W. K., Kirkup, W., Bates, D., & Edwardson, J. A. (1993) · Psychological Medicine · doi:10.1017/s0033291700025411 · Cited by 92
Alzheimer's Disease and Parkinson's Disease
(2003) · New England Journal of Medicine · doi:10.1056/nejm200306193482528 · Cited by 48
Multiple etiologies for Alzheimer disease are revealed by segregation analysis.
Rao, V. S., van Duijn, C. M., Connor-Lacke, L., Cupples, L. A., Growdon, J. H., & Farrer, L. A. (1994) · PubMed Central · Cited by 37
Heredity in dementia of the Alzheimer type
Bergem, A. L. M. (1994) · Clinical Genetics · doi:10.1111/j.1399-0004.1994.tb04216.x · Cited by 33
Prevalence and causes of young onset dementia in an English health district
Renvoize, E. B., Hanson, M., & Dale, M. C. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2456 · Cited by 31
Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease
Cruts, M. (1994) · Neurobiology of Aging · doi:10.1016/0197-4580(94)92994-7 · Cited by 9
Transmission and age-at-onset patterns in familial Alzheimer??s disease: evidence for heterogeneity
Farrer, L. A., Myers, R. H., Cupples, L. A., George-Hyslop, P. S., Bird, T. D., Rossor, M. N., MULLAN, M. J., Polinsky, R. J., Nee, L. E., Heston, L. L., et al. (1991) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199100510-00015 · Cited by 6
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Metadata
- Authors
- Wingo, T. S.
- Affiliations
- Emory University (US)
- Corresponding author
- Wingo, Thomas S.
- ORCID
- Wingo, Thomas S.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2012-01-01
- Volume
- 69
- Issue
- 1
- Pages
- 59
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3332307
- OpenAlex
- W2170959965
- Cited by
- 265
- References
- 40
- Citations by year
- 2026: 16 · 2025: 31 · 2024: 26 · 2023: 22 · 2022: 25 · 2021: 31 · 2020: 26 · 2019: 26 · 2018: 14 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 7 · 2013: 5 · 2012: 7
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alzheimer's Coordinating Center (U01AG016976)
- National Institutes of Health (UL1TR000454, AG016976, AG025688)
- National Institute on Aging (U01AG016976, P50AG025688)
- National Human Genome Research Institute (R01HG003461)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- early-onset Alzheimer's disease, late-onset Alzheimer's disease, autosomal recessive inheritance, heritability, sibling concordance, liability threshold model, polygenic inheritance
- MeSH terms
- Adult, Alzheimer Disease, Apolipoproteins E, Family Health, Female, Genotype, Humans, Male, Middle Aged, Neuropsychological Tests, Risk Factors, Cohort Studies, Age of Onset, Genetic Predisposition to Disease
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