Intrinsic functional connectivity alterations in cognitively intact elderly APOE ε4 carriers measured by eigenvector centrality mapping are related to cognition and CSF biomarkers: a preliminary study.
Apolipoprotein E (APOE) ε4 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 ε4 carriers. Thirteen cognitively intact, elderly APOE ε4 carriers and 22 ε3 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 Aβ1-42, total-tau (t-tau) and phosphorylated-tau (p-tau181) 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 ε4 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 ε4 carriers. This study suggests the APOE ε4 allele contributes to disruption of brain connectedness in certain functional nodes, which may result from neuronal death caused by toxicity of neurofibrillary tangles.
['Luo|Xiao|X|', 'Qiu|Tiantian|T|', 'Jia|Yunlu|Y|', 'Huang|Peiyu|P|', 'Xu|Xiaojun|X|', 'Yu|Xinfeng|X|', 'Shen|Zhujing|Z|', 'Jiaerken|Yerfan|Y|', 'Guan|Xiaojun|X|', 'Zhou|Jiong|J|', 'Zhang|Minming|M|http://orcid.org/0000-0003-0145-7558', '|||']
D000368:Aged D016229:Amyloid beta-Peptides D053327:Apolipoprotein E4 D015415:Biomarkers D001921:Brain D001931:Brain Mapping D003071:Cognition D003430:Cross-Sectional Studies D005260:Female D060005:Genotyping Techniques D006579:Heterozygote D006801:Humans D008297:Male D009434:Neural Pathways D009483:Neuropsychological Tests D012146:Rest D016875:tau Proteins
Functional connectivity CSF Apolipoproteins E Alzheimer disease Resting-state fMRI