Multimodal Brain Imaging Reveals Structural Differences in Alzheimer’s Disease Polygenic Risk Carriers: A Study in Healthy Young Adults

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• 作者：Sonya F. Foley^a ; ^b ; ^c ; ^{foleys2@cardiff.ac.uk} ; Katherine E. Tansey^a ; ^d ; Xavier Caseras^a ; ^b ; Thomas Lancaster^a ; ^b ; Tobias Bracht^b ; Greg Parker^b ; Jeremy Hall^a ; ^e ; Julie Williams^a ; David E.J. Linden^a ; ^b
• 关键词：Alzheimer&rsquo ; s disease ; Cingulum ; Fornix ; Hippocampus ; Imaging ; Polygenic risk
• 刊名：Biological Psychiatry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：81
• 期：2
• 页码：154-161
• 全文大小：1410 K
• 卷排序：81

文摘

Recent genome-wide association studies have identified genetic loci that jointly make a considerable contribution to risk of developing Alzheimer’s disease (AD). Because neuropathological features of AD can be present several decades before disease onset, we investigated whether effects of polygenic risk are detectable by neuroimaging in young adults. We hypothesized that higher polygenic risk scores (PRSs) for AD would be associated with reduced volume of the hippocampus and other limbic and paralimbic areas. We further hypothesized that AD PRSs would affect the microstructure of fiber tracts connecting the hippocampus with other brain areas.MethodsWe analyzed the association between AD PRSs and brain imaging parameters using T1-weighted structural (n = 272) and diffusion-weighted scans (n = 197).ResultsWe found a significant association between AD PRSs and left hippocampal volume, with higher risk associated with lower left hippocampal volume (p = .001). This effect remained when the APOE gene was excluded (p = .031), suggesting that the relationship between hippocampal volume and AD is the result of multiple genetic factors and not exclusively variability in the APOE gene. The diffusion tensor imaging analysis revealed that fractional anisotropy of the right cingulum was inversely correlated with AD PRSs (p = .009). We thus show that polygenic effects of AD risk variants on brain structure can already be detected in young adults.ConclusionsThis finding paves the way for further investigation of the effects of AD risk variants and may become useful for efforts to combine genotypic and phenotypic data for risk prediction and to enrich future prevention trials of AD.