ApoE genotype accounts for the vast majority of AD risk and AD pathology
Abstract
In this review, evidence is provided that apolipoprotein E (apoE) genotype accounts for the majority of Alzheimer's disease (AD) risk and pathology. The three major human isoforms, apoE2, apoE3, and apoE4, are encoded by different alleles (2, 3, 4) and regulate lipid metabolism and redistribution. ApoE isoforms differ in their effects on AD risk and pathology. Clinical and epidemiological data have indicated that the 4 allele may account for 50% of AD in the United States. Further, the rarity of AD among carriers of the 2 allele suggests that allelic variations in the gene encoding this protein may account for over 95% of AD cases. ApoE4 disrupts memory function in rodents. Further studies have indicated that fragments of apoE may contribute to both plaque and tangle formation. Thus, the epidemiologic and basic science evidence suggest that apoE genotype accounts for the vast majority of AD risk and pathology.
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The apoE4 allele accounts for between 50 and 60% of the genetic variation in Alzheimer's disease.
“The association of allele four of apoE (4) as a genetic risk factor for Alzheimer's disease (AD) has been well established, accounting for between 50 -60% of the genetic variation in the disease (Corder et al., 1993;Raber et al., 2004).”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Raber et al., 2004
Inheritance of the apoE4 allele increases the risk of developing Alzheimer's disease.
“Inheritance of the apoE4 allele (4) increases the risk of developing Alzheimer's disease; however, the mechanisms underlying this association remain elusive.”
From Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels (2008) · cites this paper as Raber et al., 2004
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- Authors
- Raber, J., Huang, Y., & Ashford, J. W.
- Affiliations
- Oregon Health & Science University (US)
- University of California, San Francisco (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Raber, Jacob
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 25
- Issue
- 5
- Pages
- 641-650
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2117625001
- Cited by
- 599
- References
- 11
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 26 · 2023: 25 · 2022: 33 · 2021: 24 · 2020: 32 · 2019: 31 · 2018: 38 · 2017: 34 · 2016: 31 · 2015: 36 · 2014: 16 · 2013: 44 · 2012: 19
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-17824, R01 AG 20904, P30AG017824, P01AG022074, R01AG020904, AG-NS-020-02)
- 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
- apolipoprotein E, Alzheimer's disease, APOE ε4, APOE2, APOE3, genetic risk, amyloid plaques, neurofibrillary tangles, memory impairment, lipid metabolism, genetic epidemiology
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Apolipoproteins E, Disease Models, Animal, Gene Frequency, Genotype, Humans, Memory Disorders, Risk, Sex Factors, Neurofibrillary Tangles, Genetic Predisposition to Disease, Plaque, Amyloid
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