Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
Neuroscience. 2012 Sep 18;220:41-6. doi: 10.1016/j.neuroscience.2012.06.035. Epub 2012 Jun 23.
Alzheimer's Disease (AD) is the most common cause of dementia in elderly people. The presynaptic terminal is an important site of pathological changes in AD, leading to synaptic loss in specific brain regions, such as in the cortex and hippocampus. In this study, we investigated synaptosomal-associated protein, 25-kDa (SNAP25) mRNA levels and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood leukocytes of young, healthy elderly and AD patients. mRNA quantification was performed by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) using the ΔΔC(T) method and promoter DNA methylation was quantified by mass spectrometry using the Sequenom EpiTYPER platform. We observed a significant decrease in SNAP25 expression in AD across all the three brain regions in relation to the healthy elderly subjects, suggesting impairment in synaptic function. The changes in the auditory cortex reflected those observed in the hippocampus and entorhinal cortex, the primary areas affected in AD. However, no AD-associated differences in SNAP25 promoter DNA methylation were observed suggesting that other mechanisms may be involved in mediating the observed gene expression changes.
阿尔茨海默病(AD)是老年人痴呆症最常见的原因。突触前终端是 AD 病理变化的重要部位,导致特定脑区(如皮质和海马体)的突触丧失。在这项研究中,我们研究了尸检脑组织(内嗅皮质和听觉皮质和海马体)中突触相关蛋白 25kDa(SNAP25)mRNA 水平和启动子 DNA 甲基化,以及年轻、健康的老年和 AD 患者的外周血白细胞。使用定量逆转录聚合酶链反应(qRT-PCR)和Sequenom EpiTYPER 平台,通过ΔΔC(T)方法进行了 mRNA 定量,通过质谱法进行了启动子 DNA 甲基化定量。我们观察到 AD 患者在所有三个脑区的 SNAP25 表达均显著下降,这表明突触功能受损。听觉皮质的变化反映了在海马体和内嗅皮质中观察到的变化,这是 AD 中受影响的主要区域。然而,在 SNAP25 启动子 DNA 甲基化方面未观察到 AD 相关差异,这表明可能涉及其他机制来介导观察到的基因表达变化。