title: 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.
abstract: 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.
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Zhujing
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Yerfan
authors.initials: Y
authors.lastname: Jiaerken
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Neurology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radiology, 2nd Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China. zhangminming@zju.edu.cn.
authors.forename: Minming
authors.identifier: http://orcid.org/0000-0003-0145-7558
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D003071:Cognition / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology; D009483:Neuropsychological Tests; D012146:Rest; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer disease; Apolipoproteins E; CSF; Functional connectivity; Resting-state fMRI