CLU 基因中的阿尔茨海默病风险变异与健康个体的神经效率低下有关。
Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals.
机构信息
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK; Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK; MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
出版信息
Alzheimers Dement. 2015 Oct;11(10):1144-52. doi: 10.1016/j.jalz.2014.10.012. Epub 2014 Dec 10.
INTRODUCTION
Genome-wide association studies identify rs11136000 in the CLU gene, which codes for Apolipoprotein J/Clusterin, as a significant risk variant for Alzheimer's disease (AD). However, the mechanisms by which this variant confers susceptibility remain relatively unknown.
METHODS
Eighty-five healthy Caucasian participants underwent functional magnetic resonance imaging during a working memory (WM) task and were genotyped for CLU rs11136000/APOE loci.
RESULTS
Here we show that young individuals with the CLU rs11136000 risk variant (C) have higher activation levels in memory-related prefrontal and limbic areas during a WM task. We also found subtle reductions in gray matter in the right hippocampal formation in carriers of the risk variant.
DISCUSSION
We suggest that this pattern of multimodal imaging results may reflect incipient structural differences and inefficient functional activation. This study supports accumulating evidence suggesting that genetic risk for AD affects the neural networks associated with memory in healthy individuals.
简介
全基因组关联研究鉴定出 CLU 基因中的 rs11136000 是载脂蛋白 J/ 簇蛋白的一个重要风险变异，与阿尔茨海默病（AD）的易感性相关。然而，该变异如何导致易感性的机制仍相对未知。
方法
85 名健康的白种人参与者在工作记忆（WM）任务期间接受功能磁共振成像，并对 CLU rs11136000/APOE 基因座进行基因分型。
结果
我们在此表明，在 WM 任务中，CLU rs11136000 风险变异（C）的年轻个体在与记忆相关的前额叶和边缘区域具有更高的激活水平。我们还发现，风险变异携带者的右侧海马结构中的灰质有轻微减少。
讨论
我们认为这种多模态成像结果模式可能反映了初始的结构差异和功能激活效率低下。本研究支持越来越多的证据表明，AD 的遗传风险会影响健康个体与记忆相关的神经网络。
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