Affiliation:
1. Department of Neuroscience, University of Sheffield, Sheffield, S10 2RX, United Kingdom
Abstract
Background:
Research indicates that polygenic indices of risk of Alzheimer’s disease are
linked to clinical profiles.
Objective:
Given the “genetic centrality” of the APOE gene, we tested whether this held true for both
APOE-ε4 carriers and non-carriers.
Methods:
A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited
in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split
into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models
were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and
memory, executive functioning and grey-matter volumetric maps.
Results:
PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI
patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in
ε3ε3 Aβ+ participants.
Conclusion:
The link between polygenic hazard and neurocognitive variables varies depending on
APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic
interactions.
Funder
DOD ADNI
Alzheimer's Disease Neuroimaging Initiative
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Neurology,Neurology
Cited by
2 articles.
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