Shared effects of the clusterin gene on the default mode network among individuals at risk for Alzheimer's disease

• Published in: CNS neuroscience & therapeutics 2017-05, Vol.23 (5), p.395-404
• Main Authors: Ye, Qing, Su, Fan, Shu, Hao, Gong, Liang, Xie, Chun‐Ming, Zhou, Hong, Zhang, Zhi‐Jun, Bai, Feng
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Alzheimer's disease; Apolipoprotein E4 - genetics; Brain - diagnostic imaging; Brain - physiopathology; Brain Mapping; clusterin; Clusterin - genetics; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - genetics; Cognitive Dysfunction - physiopathology; default mode network; Depressive Disorder - diagnostic imaging; Depressive Disorder - genetics; Depressive Disorder - physiopathology; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genetic Variation; Genotyping Techniques; geriatric depression; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Memory, Episodic; mild cognitive impairment; Neural Pathways - physiopathology; Neuropsychological Tests; Original; Rest
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.12682

Summary Aims To explore the common effects of the clusterin (CLU) rs11136000 variant on the default mode network (DMN) in amnestic mild cognitive impairment (aMCI) subjects and remitted geriatric depression (RGD) subjects. Methods Fifty‐one aMCI subjects, 38 RGD subjects, and 64 cognitively normal elderly subjects underwent resting‐state fMRI scans and neuropsychological tests at both baseline and a 35‐month follow‐up. Posterior cingulate cortex seed‐based functional connectivity (FC) analysis was used to obtain the DMN patterns. Results A CLU gene×disease×time interaction for aMCI subjects was mainly detected in the core cortical midline structures of the DMN, and the interaction for RGD subjects was mainly detected in the limbic system. However, they overlapped in two frontal regions, where consistent effects of the CLU gene on FC alterations were found between aMCI and RGD groups. Furthermore, the alterations of FC with frontal, parietal, and limbic regions compensated for episodic memory impairments in CLU‐CT/TT carriers, while no such compensation was found in CLU‐CC carriers. Conclusion The CLU gene could consistently affect the DMN FC with frontal regions among individuals at risk for Alzheimer's disease, and the CLU‐T allele was associated with more compensatory neural processes in DMN changes.