APOE ε4 gene dose drives a canonical and predictable topography of amyloid deposition
Related Experiment Video
Updated: Oct 31, 2026

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
Augusto J Mendes1,2, Cecilia Boccalini3, Federica Ribaldi1,2
1Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
Introduction:
Apolipoprotein E ε4 (APOE ε4) carriership is associated with higher amyloid burden in Alzheimer's disease (AD), but whether it constrains the spatial predictability of amyloid deposition at the individual level remains unknown.
Methods:
We analyzed voxel-wise amyloid positron emission tomography data from 781 amyloid-positive individuals across two independent cohorts (Alzheimer's Disease Neuroimaging Initiative and Geneva Memory Center), spanning the full clinical continuum. Individual topographic similarity to canonical AD amyloid maps and within-group spatial homogeneity were assessed via voxel-wise correlations and linear regression adjusted for age, sex, and global amyloid burden.
Results:
APOE ε4 carriers exhibited amyloid distributions more aligned with canonical AD topographies than non-carriers (p < 0.001), with a clear gene-dose effect on within-group spatial homogeneity: Homozygotes showed the highest inter-subject consistency, followed by heterozygotes and non-carriers. Effects were robust across tracers, clinical stages, and cohorts.
Discussion:
APOE ε4 gene dose constrains the spatial predictability of amyloid accumulation, informing genotype-stratified approaches in anti-amyloid trials.
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