Cited by 50Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsGenetic Associations and Epidemiology

The Proportion of APOE4 Carriers Among Non-Demented Individuals: A Pooled Analysis of 389,000 Community-Dwellers

Wang, Ya-Yu, Ge, Yi-Jun, Tan, Chen-Chen, Cao, Xi-Peng, Tan, Lan, Xu, Wei·2021·Journal of Alzheimer's Disease

Abstract

Background: The apolipoprotein E epsilon 4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). Its carriage percentage in non-demented population varies across geographic regions and ethnic groups. Objective: To estimate the proportion of APOE4 (2/4, 3/4, or 4/4) carriers in non-demented community-dwellers. Methods: PubMed, EMBASE, and China National Knowledge Infrastructure were searched from inception to April 20, 2020. Community-based studies that reported APOE polymorphisms with a sample of≥500 non-demented participants were included. Random-effects models were used to pool the results. Meta-regression and subgroup analyses were performed to test the source of heterogeneity and stratified effects. Age-standardized pooled proportion estimates (ASPPE) were calculated by direct standardization method. Results: A total of 121 studies were included, with a pooled sample of 389,000 community-dwellers from 38 countries. The global average proportion of APOE4 carriers was 23.9% (age-standardized proportion: 26.3%; 2.1% for APOE4/4, 20.6% for APOE3/4 and 2.3% for APOE2/4), and varied significantly with geographical regions (from 19.3% to 30.0%) and ethnic groups (from 19.1% to 37.5%). The proportion was highest in Africa, followed by Europe, North America, Oceania, and lowest in South America and Asia (p < 0.0001). With respect to ethnicity, it was highest in Africans, followed by Caucasians, and was lowest in Hispanics/Latinos and Chinese (p < 0.0001). Conclusion: APOE4 carriers are common in communities, especially in Africans and Caucasians. Developing precision medicine strategies in this specific high-risk population is highly warranted in the future.

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Crossref · 10.3233/jad-201606

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Authors
Wang, Y.-Y., Ge, Y.-J., Tan, C.-C., Cao, X.-P., Tan, L., & Xu, W.
Affiliations
  • Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China
  • Qingdao University (CN)
Corresponding author
Xu, Wei
Venue
Journal of Alzheimer's Disease
Published
2021-06-01
Volume
81
Issue
3
Pages
1331-1339
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
OpenAlex
W3157168630
Cited by
49
References
40
Citations by year
2026: 11 · 2025: 15 · 2024: 10 · 2023: 9 · 2022: 3 · 2021: 1
FWCI
4.31
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
APOE ε4, apolipoprotein E
MeSH terms
Alleles, Alzheimer Disease, Heterozygote, Humans, Polymorphism, Single Nucleotide, Databases, Genetic, Apolipoprotein E4

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