Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia.
J Alzheimers Dis. 2024;99(s2):S235-S248. doi: 10.3233/JAD-230872.
Extracellular vesicles (EVs) and non-coding RNAs (ncRNAs) are emerging contributors to Alzheimer's disease (AD) pathophysiology. Differential abundance of ncRNAs carried by EVs may provide valuable insights into underlying disease mechanisms. Brain tissue-derived EVs (bdEVs) are particularly relevant, as they may offer valuable insights about the tissue of origin. However, there is limited research on diverse ncRNA species in bdEVs in AD.
This study explored whether the non-coding RNA composition of EVs isolated from post-mortem brain tissue is related to AD pathogenesis.
bdEVs from age-matched late-stage AD patients (n = 23) and controls (n = 10) that had been separated and characterized in our previous study were used for RNA extraction, small RNA sequencing, and qPCR verification.
Significant differences of non-coding RNAs between AD and controls were found, especially for miRNAs and tRNAs. AD pathology-related miRNA and tRNA differences of bdEVs partially matched expression differences in source brain tissues. AD pathology had a more prominent association than biological sex with bdEV miRNA and tRNA components in late-stage AD brains.
Our study provides further evidence that EV non-coding RNAs from human brain tissue, including but not limited to miRNAs, may be altered and contribute to AD pathogenesis.
细胞外囊泡（EVs）和非编码 RNA（ncRNAs）是阿尔茨海默病（AD）病理生理学中的新兴贡献者。EV 携带的 ncRNA 的差异丰度可能为潜在的疾病机制提供有价值的见解。脑源性 EV（bdEV）特别相关，因为它们可能提供有关起源组织的有价值的信息。然而，关于 AD 中 bdEV 中不同 ncRNA 种类的研究有限。
本研究探讨了从死后脑组织中分离的 EV 的非编码 RNA 组成是否与 AD 发病机制有关。
使用我们之前研究中已分离和表征的年龄匹配的晚期 AD 患者（n = 23）和对照（n = 10）的 bdEV 进行 RNA 提取、小 RNA 测序和 qPCR 验证。
AD 和对照组之间存在显著差异的非编码 RNA，尤其是 miRNA 和 tRNA。bdEV 的 AD 病理学相关 miRNA 和 tRNA 差异与源脑组织中的表达差异部分匹配。AD 病理学与晚期 AD 大脑中的 bdEV miRNA 和 tRNA 成分的关系比生物学性别更密切。
我们的研究进一步证明了来自人脑组织的 EV 非编码 RNA，包括但不限于 miRNA，可能发生改变并有助于 AD 发病机制。
