Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana.
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana.
Alzheimers Dement. 2020 Sep;16(9):1213-1223. doi: 10.1002/alz.12092. Epub 2020 Aug 5.
Abnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer's disease (LOAD).
We performed transcriptome-wide meta-analysis (N = 1440) of blood-based microarray gene expression profiles as well as neuroimaging and cerebrospinal fluid (CSF) endophenotype analysis.
We identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (Aβ) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P < 5 × 10 ), where rs56388170 (most significant) was also significantly associated with global cortical Aβ deposition measured by [ F]Florbetapir positron emission tomography and CSF Aβ .
RNA from peripheral blood indicated a differential gene expression pattern in LOAD. Genes identified have been implicated in biological processes relevant to Alzheimer's disease. CREB, in particular, plays a key role in nervous system development, cell survival, plasticity, and learning and memory.
异常的基因表达模式可能导致晚期阿尔茨海默病（LOAD）的发生和发展。
我们对基于血液的微阵列基因表达谱进行了全转录组荟萃分析（N=1440），以及神经影像学和脑脊液（CSF）内表型分析。
我们鉴定并复制了五个在 LOAD 中明显失调的基因（CREB5、CD46、TMBIM6、IRAK3 和 RPAIN）。变化最显著的基因 CREB5 也与脑萎缩和淀粉样β（Aβ）积累增加有关，特别是在内嗅皮层区域。CREB5 的顺式表达数量性状基因座作图分析检测到五个显著关联（P<5×10），其中 rs56388170（最显著）也与通过[F]Florbetapir 正电子发射断层扫描和 CSF Aβ 测量的全局皮质 Aβ沉积显著相关。
外周血中的 RNA 表明 LOAD 存在差异的基因表达模式。已鉴定的基因与阿尔茨海默病相关的生物学过程有关。特别是 CREB 在神经系统发育、细胞存活、可塑性以及学习和记忆中起着关键作用。
