title: Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study.
abstract: Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer's disease. Previous neuroimaging studies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease.
authors.affiliation: School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi 710071, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Medical Biotechnology, Dongguk University, 21 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi 710071, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi 710071, China.
authors.forename: Junchan
authors.initials: J
authors.lastname: Ren
authors.affiliation: MGB, 291, Harmony-ro, Yeonsu-gu, Incheon, Republic of Korea.
authors.forename: Min Seob
authors.initials: MS
authors.lastname: Lee
authors.affiliation: EDGC, 291, Harmony-ro, Yeonsu-gu, Incheon, Republic of Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi 710071, China. Electronic address: huangly@mail.xidian.edu.cn.
authors.forename: Liyu
authors.initials: L
authors.lastname: Huang
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D005260:Female; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D000073216:Mental Status and Dementia Tests; D064847:Multimodal Imaging; D059906:Neuroimaging; D009483:Neuropsychological Tests; D009929:Organ Size; D012146:Rest; D066127:White Matter / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D053327:Apolipoprotein E4
keywords: APOE ε4; Alzheimer’s disease; Cognitively intact elderly; DTI; Gray matter activity; MRI; White matter integrity; fMRI