Apolipoprotein E Genetic Variation and Alzheimer’s Disease
Abstract
In order to quantify the effects of apolipoprotein (apo) E on early- and late-onset, sporadic and familial Alzheimer’s disease (AD) more precisely we performed a meta-analysis of 42 case-control series published before July 1996. We excluded studies of late-onset AD with fewer than 50 cases and 50 controls. The estimated odds ratio of AD over the age of 65 years associated with the apo ε4 allele, relative to apo ε3, was 3.18 (95% CI 2.93–3.45, p < 0.00001). Apo ε4 was associated with a significantly higher relative risk of early-onset disease (<65 years) unselected for family history (OR 4.86, 95% CI 3.61–6.54, p < 0.0001), but its impact on early-onset familial disease was weaker (OR 1.48, 95% CI 1.02–2.16). The estimated odds ratio associated with the ε4/ε4 genotype, relative to the ε3/ε3 genotype, was 11.57 (95% CI 8.67–15.44) for all cases over 65 and 61.44 (95% CI 13.47–280.3) for early-onset disease unselected for family history. Apo ε2 was associated with a significantly reduced odds ratio for AD above the age of 65 (OR 0.68, 95% CI 0.58–0.80, p < 0.00001), but not in familial early-onset AD, where apo ε2 may be associated with an increased risk (OR 1.70, 95% CI 1.02–2.84). We estimate that 60% (95% CI 48–68%) of AD cases over the age of 65 years and 92% of cases below the age of 65 would be attributable to apo E and that apo E probably accounts for less than 50% of the familial aggregation of the disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer's disease (AD).
“The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD).”
From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [6]
Cites
Apolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981 · see citing works
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 · see citing works
Genetic associations with human longevity at the APOE and ACE loci
Schächter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., & Cohen, D. (1994) · Nature Genetics · doi:10.1038/ng0194-29 · Cited by 1,095 · see citing works
A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism
Kamboh, M. I., Sanghera, D. K., Ferrell, R. E., & DeKosky, S. T. (1995) · Nature Genetics · doi:10.1038/ng0895-486 · Cited by 336 · see citing works
Protection against Alzheimer's disease with apoE ∈2
Talbot, C., Lendon, C., Craddock, N., Shears, S., Morris, J., & Goate, A. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92557-7 · Cited by 225 · see citing works
The presenilin genes: a new gene family involved in Alzheimer disease pathology
Cruts, M., Hendriks, L., & Van Broeckhoven, C. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.supplement_1.1449 · Cited by 163 · see citing works
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Brain Cholesterol: Long Secret Life Behind a Barrier
Björkhem, I., & Meaney, S. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000120374.59826.1b · Cited by 1,044 · see citing works
A HapMap harvest of insights into the genetics of common disease
Manolio, T. A., Brooks, L. D., & Collins, F. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34772 · Cited by 889 · see citing works
Genetics of Alzheimer’s disease: An East Asian perspective
Miyashita, A., Kikuchi, M., Hara, N., & Ikeuchi, T. (2023) · Journal of Human Genetics · doi:10.1038/s10038-022-01050-z · Cited by 64 · see citing works
Area-Gomez, E., Larrea, D., Pera, M., Agrawal, R. R., Guilfoyle, D. N., Pirhaji, L., Shannon, K., Arain, H. A., Ashok, A., Chen, Q., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61142-8 · Cited by 55 · see citing works
Cluett, C., Brayne, C., Clarke, R., Evans, G., Matthews, F., Rubinsztein, D. C., Huppert, F., Llewellyn, D. J., Rice, N., Henley, W., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.020 · Cited by 12 · see citing works
Self-citation
- Authors
- Rubinsztein, D. C., & Easton, D. F.
- Affiliations
- Addenbrooke's Hospital (GB)
- University of Cambridge (GB)
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 1999
- Volume
- 10
- Issue
- 3
- Pages
- 199-209
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W2012355806
- Cited by
- 151
- References
- 7
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 7 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 8 · 2014: 3 · 2013: 12 · 2012: 3
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- apolipoprotein E, Alzheimer's disease, APOE ε4, APOE ε2 allele, APOE ε3 allele, early-onset Alzheimer's disease, late-onset Alzheimer's disease, familial Alzheimer's disease, genetic risk, attributable risk, familial aggregation
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Cross-Sectional Studies, Genotype, Humans, Genetic Variation
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
