Department of Morphology & Genetics, Universidade Federal de São Paulo (UNIFESP), São Paulo,SP, 04023-062, Brazil.
Department of Environmental Health & Molecular & Integrative Physiological Sciences Program, Harvard TH Chan School of Public Health, Boston, MA 02115-5810, USA.
Epigenomics. 2022 Jun;14(11):651-670. doi: 10.2217/epi-2022-0096. Epub 2022 May 19.
To evaluate H3K9 acetylation and gene expression profiles in three brain regions of Alzheimer's disease (AD) patients and elderly controls, and to identify AD region-specific abnormalities. Brain samples of auditory cortex, hippocampus and cerebellum from AD patients and controls underwent chromatin immunoprecipitation sequencing, RNA sequencing and network analyses. We found a hyperacetylation of AD cerebellum and a slight hypoacetylation of AD hippocampus. The transcriptome revealed differentially expressed genes in the hippocampus and auditory cortex. Network analysis revealed Rho GTPase-mediated mechanisms. These findings suggest that some crucial mechanisms, such as Rho GTPase activity and cytoskeletal organization, are differentially dysregulated in brain regions of AD patients at the epigenetic and transcriptomic levels, and might contribute toward future research on AD pathogenesis.
为了评估阿尔茨海默病(AD)患者和老年对照组三个大脑区域的 H3K9 乙酰化和基因表达谱,并确定 AD 区域特异性异常,我们对 AD 患者和对照组的听觉皮层、海马体和小脑的脑组织进行了染色质免疫沉淀测序、RNA 测序和网络分析。我们发现 AD 小脑组织存在乙酰化过度,AD 海马组织存在轻微的乙酰化不足。转录组显示在海马体和听觉皮层中存在差异表达的基因。网络分析揭示了 Rho GTPase 介导的机制。这些发现表明,在 AD 患者的大脑区域,一些关键机制,如 Rho GTPase 活性和细胞骨架组织,在表观遗传和转录组水平上存在差异失调,这可能为 AD 发病机制的未来研究做出贡献。