The TT allele of rs405509 synergizes with APOE ε4 in the impairment of cognition and its underlying default mode network in non-demented elderly

Background: Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 as the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer’s disease (AD). However, it is unclear the APOE-rs405509 interaction effect on brain spontaneous activity. Methods: We analyzed the interaction of the rs405509 TT allele and the APOE ε4 allele on cognitive performances measured using neuropsychological tests and brain default mode network (DMN) defined by independent component analysis using based on resting-state functional magnetic resonance imaging data among the non-demented elderly people. Results: Significant interaction was found between rs405509 and APOE on general mental status, memory and attention (p<0.05). Functional network analysis showed a significantly APOE-rs405509 interaction on anterior cingulate gyrus, medial frontal region and precuneus at anterior and posterior DMN (False Discovery Rate p<0.05). Additionally, significant correlations were found between cognitive performance and DMN connectivity (p<0.05). Conclusion: The data indicates that the APOE-rs405509 interaction impairs elderly’s cognitive performance through brain functional network.