Association of a GSK-3β Polymorphism with Brain Resting-State Function in Amnestic-Type Mild Cognitive Impairment

Article type: Research Article

Authors: Bai, Feng^{a; b} | Shi, Yongmei^a | Yuan, Yonggui^a | Yue, Chunxian^b | Zhuang, Liying^b | Xu, Xiaohui^b | Liu, Xiaoyan^b | Zhang, Zhijun^{a; *}

Affiliations: [a] Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, and The Institute of Neuropsychiatry of Southeast University, Nanjing, China | [b] Medical School of Southeast University, Nanjing, China

Correspondence: [*] Correspondence to: Zhi-jun Zhang, Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, and The Institute of Neuropsychiatry of Southeast University, Nanjing 210009, China. Tel.: +86 25 83272023; Fax: +86 25 2583285132; E-mail: [email protected].

Abstract: The glycogen synthase kinase-3β (GSK-3β) gene has been implicated in Alzheimer's disease (AD). Polymorphisms in this gene are plausible modulators of brain function. However, little is known about the potential role of the GSK-3β rs334558 polymorphism, which has been associated with amnestic mild cognitive impairment (aMCI), which is itself associated with a high risk of AD. In this study, 43 aMCI patients and 30 healthy controls underwent resting-state functional magnetic resonance imaging, and their GSK-3β rs334558 genotypes were evaluated to determine the effect of the risk variant on regional brain activity and functional networks in these subjects. Then, gene-brain-behavior relationships were examined. Compared with the controls, aMCI subjects with the higher risk T allele had more deficits in regional activation of the right superior frontal gyrus (rSFG), while a higher functional connectivity of the rSFG was observed in TT/CT carriers. Further correlative analyses revealed that the increase in rSFG connectivity was robustly positively correlated with non-memory performance in aMCI GSK-3β rs334558 TT/CT carriers. Our findings are the first to show that a clinically significant proportion of resting-state brain function variation in aMCI patients may be explained by genetic variation at the GSK-3βrs334558 locus in ways that are distinguishable from controls.

Keywords: Brain function, functional magnetic resonance imaging, genetic imaging, glycogen synthase kinase, mild cognitive impairment, resting state

DOI: 10.3233/JAD-2012-120631

Journal: Journal of Alzheimer's Disease, vol. 32, no. 2, pp. 387-396, 2012