Interactions between GSK3β and amyloid genes explain variance in amyloid burden

NEUROBIOLOGY OF AGING

卷:35

Article

Hohman, Timothy J.¹  Koran, Mary Ellen I.¹  Thornton-Wells, Tricia A.¹ 

[1] Vanderbilt Univ, Sch Med, Ctr Human Genet & Res, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA

关键词: Imaging genetics;    Alzheimer's disease;    Amyloid;    Tau;    PET;    ADNI;   

DOI  :  10.1016/j.neurobiolaging.2013.08.032

来源: Elsevier

【 摘 要 】

The driving theoretical framework of Alzheimer's disease (AD) has been built around the amyloid-beta (A beta) cascade in which amyloid pathology precedes and drives tau pathology. Other evidence has suggested that tau and amyloid pathology may arise independently. Both lines of research suggest that there may be epistatic relationships between genes involved in amyloid and tau pathophysiology. In the current study, we hypothesized that genes coding glycogen synthase kinase 3 (GSK-3) and comparable tau kinases would modify genetic risk for amyloid plaque pathology. Quantitative amyloid positron emission tomography data from the Alzheimer's Disease Neuroimaging Initiative served as the quantitative outcome in regression analyses, covarying for age, gender, and diagnosis. Three interactions reached statistical significance, all involving the GSK3 beta single nucleotide polymorphism rs334543-2 with APBB2 (rs2585590, rs3098914) and 1 with APP (rs457581). These interactions explained 1.2%, 1.5%, and 1.5% of the variance in amyloid deposition respectively. Our results add to a growing literature on the role of GSK-3 activity in amyloid processing and suggest that combined variation in GSK3 beta and APP-related genes may result in increased amyloid burden. (C) 2014 Elsevier Inc. All rights reserved.

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