Intrinsic functional connectivity alterations in cognitively intact elderly APOE epsilon 4 carriers measured by eigenvector centrality mapping are related to cognition and CSF biomarkers: a preliminary study

摘要

Apolipoprotein E (APOE) epsilon 4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older epsilon 4 carriers. Thirteen cognitively intact, elderly APOE epsilon 4 carriers and 22 epsilon 3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI). We evaluated comprehensive cognitive ability and tested levels of A beta(1-42), total-tau (t-tau) and phosphorylated-tau (p-tau(181)) in CSF. Comparisons of ECM between two groups were conducted, followed by correlations analyses between EC values with significant group differences and cognitive ability/CSF biomarkers. APOE epsilon 4 carriers showed significantly decreased EC values in left medial temporal lobe (MTL), left lingual gyrus (LG) and increased EC values in left middle frontal gyrus (MFG) as compared to non-carriers. Correlation analysis demonstrated that left LG EC value correlated with Rey Auditory Verbal Learning Test total learning (RAVLT, r = 0.57, p < 0.05) and t-tau level (r = -0.57, p < 0.05), while left MFG EC values correlated with log-transformed Trail-Making Test B (TMT-B, r = -0.67, p < 0.05) in APOE epsilon 4 carriers. This study suggests the APOE epsilon 4 allele contributes to disruption of brain connectedness in certain functional nodes, which may result from neuronal death caused by toxicity of neurofibrillary tangles.