Aims

Epigenetic regulation plays an important role in the progression of Alzheimer's disease (AD). Here, we identified differential methylation probes (DMP) and investigated their potential mechanistic roles in AD.

Main methods

DMPs were identified via bioinformatic analysis of GSE66351, which was made up with 106 AD samples and 84 control samples derived from three separate brain regions. Differentially expressed genes (DEGs) were analyzed based on GSE5281 comprising 45 control samples and 58 AD samples. Gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) were used to identify pathways and hub genes.

Key findings

We found 9007 DMPs in Occipital Cortex glia, 1527 in OC neurons, 100 in Temporal Cortex, and 194 in Frontal Cortex. 74 DEGs were identified in Primary Visual Cortex, 67 of which were downregulated while seven upregulated. 482 were upregulated and 697 downregulated in medial temporal gyrus. In superior frontal gyrus, 687 were upregulated and 85 downregulated. GO and PPI revealed that pathways involving epithelial-cell differentiation, cellular responses to lipids, transcription corepressor activities, apoptotic and organ growth were modulated by histone deacetylase 1 (HDAC1) and associated with AD. Additionally, GSEA illustrated that the transforming growth factor beta signaling pathway was significantly enriched in some brain regions and HDAC1 played an important role in this pathway.

Significance

We found the glial-specific 3′UTR of HDAC1 was hypermethylated and HDAC1 was overexpressed in AD patients. Moreover, we also speculate that HDAC1 triggered signaling pathways linked to many different biological processes and functions via the regulation of histone deacetylation.

中文翻译：

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组蛋白脱乙酰基酶1的神经胶质特异性超甲基化3'非翻译区可能调节阿尔茨海默氏病的几个信号通路

目的

表观遗传调控在阿尔茨海默氏病（AD）的进展中起着重要作用。在这里，我们确定了差异甲基化探针（DMP），并研究了它们在AD中的潜在作用。

主要方法

通过GSE66351的生物信息学分析鉴定了DMP，GSE66351由来自三个不同大脑区域的106个AD样品和84个对照样品组成。基于包含45个对照样品和58个AD样品的GSE5281分析差异表达基因（DEG）。基因本体论（GO），基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）用于鉴定途径和中心基因。

主要发现

我们在枕皮质胶质细胞中发现了9007个DMP，在OC神经元中发现了1527个，在颞皮质中发现了100个，额叶皮质中发现了194个DMP。在初级视觉皮层中鉴定出74个DEG，其中67个被下调而七个被上调。内侧颞回中有482个上调，而697个下调。在额上回中，上调了687个，下调了85个。GO和PPI显示，涉及上皮细胞分化，对脂质的细胞反应，转录共抑制物活性，凋亡和器官生长的途径受组蛋白脱乙酰基酶1（HDAC1）调节，并与AD相关。此外，GSEA表明，转化生长因子β信号转导途径在某些脑区中显着丰富，而HDAC1在该途径中起着重要作用。

意义

我们发现AD患者中HDAC1的神经胶质特异性3'UTR甲基化，HDAC1过表达。此外，我们还推测，HDAC1通过调节组蛋白脱乙酰基作用触发了与许多不同的生物学过程和功能相关的信号通路。