Apolipoprotein E moderates the association between Non-APOE Polygenic Risk Score for Alzheimer's Disease and Aging on
Yuexuan Xu1, Zhongxuan Sun2, Erin Jonaitis3,4
1Department of Population Health Science, School of Medicine and Public Health, University of Wisconsin-Madison.
Introduction:
Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (e.g., a non-APOE polygenic risk scores [PRS]) may interact with the APOE ε4 allele to influence cognitive decline.
Methods:
We tested the PRS×APOE ε4×age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjusted for within individual/family correlation among 1,190 individuals.
Results:
We found statistically significant PRS×APOE ε4×age interactions on immediate learning (P=0.038), delayed recall (P<0.001), and Preclinical Alzheimer's Cognitive Composite 3 score (P=0.026). PRS-related differences in overall and memory-related cognitive domains between people with and without APOE ε4 emerge around age 70, with a much stronger adverse PRS effect among APOE ε4 carriers. The findings were replicated in a population-based cohort.
Discussion:
APOE ε4 can modify the association between PRS and cognition decline.
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