The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype

Author(s): Matteo De Marco, Riccardo Manca, Janine Kirby, Guillaume M. Hautbergue, Daniel J. Blackburn, Stephen B. Wharton, Annalena Venneri*, Alzheimer’s Disease Neuroimaging Initiative

Journal Name: Current Alzheimer Research

Volume 17 , Issue 7 , 2020

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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.

Keywords: Mild cognitive impairment, apolipoprotein, memory, executive function, polygenic traits, amyloid.

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Year: 2020
Page: [667 - 679]
Pages: 13
DOI: 10.2174/1567205017666201006161800
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