Genotypic effects of APOE-ε4 on resting-state connectivity in cognitively intact individuals support functional brain compensation.

ABSTRACT: The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the ε4 allele. Yet, no study has assessed APOE-ε4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-ε4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of ε4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found

SUBMITTER: Cacciaglia R 

PROVIDER: S-EPMC10016049 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature