Refining Risk for Alzheimer's Disease Among Heterozygous APOEɛ4 Carriers

In a large population-based cohort, we show not all heterozygous APOEɛ4 carriers are at increased risk for Alzheimer's disease (AD); a significantly higher AD proportion was only found for ɛ3/ɛ4, not ɛ2/ɛ4. Among ɛ3/ɛ4 carriers (24% in the cohort), the AD proportion differed considerably by pol...

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Bibliographic Details
Published inJournal of Alzheimer's disease Vol. 94; no. 2; p. 483
Main Authors Patel, Smita, Wei, Jun, Shi, Zhuqing, Rifkin, Andrew S, Zheng, S Lilly, Gelfman, Elizabeth, Duggan, David, Helfand, Brian T, Hulick, Peter J, Xu, Jianfeng
Format Journal Article
LanguageEnglish
Published Netherlands 2023
Subjects
Alzheimer Disease - genetics
Apolipoprotein E4 - genetics
Apolipoproteins E - genetics
Heterozygote
Homozygote
Humans
genetic counseling
APOE
Alzheimer’s disease
UK Biobank
polygenic risk score
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Summary:In a large population-based cohort, we show not all heterozygous APOEɛ4 carriers are at increased risk for Alzheimer's disease (AD); a significantly higher AD proportion was only found for ɛ3/ɛ4, not ɛ2/ɛ4. Among ɛ3/ɛ4 carriers (24% in the cohort), the AD proportion differed considerably by polygenic risk score (PRS). In particular, the AD proportion was lower than the entire cohort for subjects in the bottom 20-percentile PRS and was higher than that of homozygous ɛ4 carriers for subjects at the top 5th-percentile PRS. Family history was no longer a significant predictor of AD risk after adjusting APOE and PRS.
ISSN:1875-8908
DOI:10.3233/JAD-230156