Impact of APOE on amyloid progression in Alzheimer disease

Abstract

AbstractBackgroundIt is well recognized that β‐amyloid (Aβ) pathology plays an important role in Alzheimer Disease (AD) pathophysiology. The amount of Aβ in the brain varies substantially within both preclinical and symptomatic AD populations. Part of this inter‐individual variability in amyloid pathology may be explained by the genotype variation of Apolipoprotein E (APOE), with the allele e4 found to be the most significant genetic risk factor for late‐onset AD. However, the impact of APOE genotype on the rate of amyloid accumulation is less clear and requires further investigation. In this study, we focus on longitudinal approaches to investigate how APOE genotype influences the trajectories of the Aβ pathology.MethodFor this project, we used longitudinal data of participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Washington University Knight Alzheimer Disease Research Center (Knight ADRC). We included 247 participants with available APOE genotype data, and longitudinal measure of Aβ burden via florbetapir (AV45) PET data, see table 1. Imaging PET data from ADNI and ADRC were harmonized using a centiloid conversion. The rate of Aβ accumulation was estimated as the slope of the random coefficient model using all available time points of longitudinal imaging data for each participant, controlling for age, sex, education and cohort. Generalized linear model was used to test the association between APOE genotype and the rate of change in amyloid.ResultThe rate of change in amyloid burden was not significantly different among all APOE genotype groups (Figure 1A; F = 1.64, p = 0.15). When looking specifically at the effect of allele count for APOE‐e4, we observed the rate of change in amyloid burden increased with e4 allele (Figure 1B; F = 4.18, P = 0.02). Pairwise comparison showed significant differences in rate of amyloid accumulation between e4e4 and e2e3 APOE genotype groups (p = 0.04), and between e4e4 and e3e3 APOE genotype groups (p = 0.04), see table 2. There was no significant difference in rate of amyloid accumulation between other genotype groups.ConclusionAPOE e4 increases AD risk by accelerating the amyloid deposition. Future direction will include a larger sample size to investigate the effect of e2 and e3 on amyloid progression in AD.