Gene Expression of Quaking in Sporadic Alzheimer's Disease Patients is Both Upregulated and Related to Expression Levels of Genes Involved in Amyloid Plaque and Neurofibrillary Tangle Formation
Gene Expression of Quaking in Sporadic Alzheimer's Disease Patients is Both Upregulated and Related to Expression Levels of Genes Involved in Amyloid Plaque and Neurofibrillary Tangle Formation
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DOI：
10.3233/jad-160160
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Emilsson, Lina Sors
中科院分区：
文献类型：
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作者：
Farnsworth, Bryn;Peuckert, Christiane;Emilsson, Lina Sors
Quaking（QKI）是一种仅在神经胶质细胞内表达的基因。QKI先前已涉及各种神经系统疾病和疾病，包括阿尔茨海默病（AD），越来越多的证据表明神经胶质细胞的核心作用。本研究的目的是研究QKI和三种QKI亚型（QKI 5，QKI 6和QKI 7）在AD中的表达水平。还研究了先前与AD的个体发生和进展相关的基因，特别是APP、PSEN1、PSEN2和MAPT。对123份来自人类尸检散发性AD患者和对照脑的样本进行实时PCR分析。采用协方差分析模型和随后的多元回归分析表达值，以探索QKI、QKI亚型和AD相关基因之间相关表达值的可能性。此外，分析AD相关基因的序列中QKI结合结构域的存在。发现相对于对照样本，AD样本中QKI和所有测量的QKI亚型均显着上调。然而，APP、PSEN1、PSEN2和MAPT没有发现显著差异。发现QKI和QKI亚型预测APP、PSEN1、PSEN2和MAPT的变化，并且推定的QKI结合位点表明与QKI的相互作用。总的来说，这些结果暗示了QKI在AD中的可能作用，尽管这种情况发生的确切机制仍有待揭示。
Quaking (QKI) is a gene exclusively expressed within glial cells. QKI has previously been implicated in various neurological disorders and diseases, including Alzheimer's disease (AD), a condition for which increasing evidence suggests a central role of glia cells. The objective of the present study was to investigate the expression levels of QKI and three QKI isoforms (QKI5, QKI6, and QKI7) in AD. Genes that have previously been related to the ontogeny and progression of AD, specifically APP, PSEN1, PSEN2, and MAPT, were also investigated. A real-time PCR assay of 123 samples from human postmortem sporadic AD patients and control brains was performed. The expression values were analyzed with an analysis of covariance model and subsequent multiple regressions to explore the possibility of related expression values between QKI, QKI isoforms, and AD-related genes. Further, the sequences of AD-related genes were analyzed for the presence of QKI binding domains. QKI and all measured QKI isoforms were found to be significantly upregulated in AD samples, relative to control samples. However, APP, PSEN1, PSEN2, and MAPT were not found to be significantly different. QKI and QKI isoforms were found to be predictive for the variance of APP, PSEN1, PSEN2, and MAPT, and putative QKI binding sites suggests an interaction with QKI. Overall, these results implicate a possible role of QKI in AD, although the exact mechanism by which this occurs remains to be uncovered.