The TT allele of rs405509 synergizes with APOE 4 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 4 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.