Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
J Alzheimers Dis. 2014;38(1):165-70. doi: 10.3233/JAD-130428.
Alzheimer's disease (AD) is the most common form of dementia in elderly. Chaperones may have a crucial role in AD due to their involvement in protein quality control, folding, and degradation. In this study, we investigated the mRNA and promoter DNA methylation levels of two chaperones, HSPA8 and HSPA9, in postmortem brain tissue (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood of healthy elderly and AD patients. mRNA quantification was performed by qRT-PCR and DNA methylation by mass spectrometry. In the peripheral blood, we did not observe a significant difference in HSPA8 and HSPA9 expression between elderly controls and AD. A significant downregulation of HSPA8 and HSPA9 was observed in AD across the three brain regions compared to the controls, suggesting their participation in AD pathogenesis. However, no important DNA methylation differences were observed, suggesting that other mechanism may be involved in controlling these genes expression.
阿尔茨海默病（AD）是老年人中最常见的痴呆症形式。伴侣蛋白可能在 AD 中发挥关键作用，因为它们参与蛋白质质量控制、折叠和降解。在这项研究中，我们研究了两种伴侣蛋白 HSPA8 和 HSPA9 的 mRNA 和启动子 DNA 甲基化水平，这些蛋白存在于健康老年人和 AD 患者的死后脑组织（内嗅皮质和听觉皮质及海马体）以及健康老年人和 AD 患者的外周血中。通过 qRT-PCR 进行 mRNA 定量，通过质谱法进行 DNA 甲基化。在外周血中，我们没有观察到 HSPA8 和 HSPA9 在老年对照组和 AD 组之间的表达存在显著差异。与对照组相比，AD 患者在三个脑区的 HSPA8 和 HSPA9 表达明显下调，表明它们参与了 AD 的发病机制。然而，没有观察到重要的 DNA 甲基化差异，这表明可能存在其他机制来控制这些基因的表达。
