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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2174/1567205017666201006161800 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!