Small RNA Profiles of Brain Tissue-Derived Extracellular Vesicles in Alzheimer's Disease

Yiyao Huang, Tom A P Driedonks, Lesley Cheng, Andrey Turchinovich, Olga Pletniková, Javier Redding-Ochoa, Juan C Troncoso, Andrew F Hill, Vasiliki Mahairaki, Lei Zheng, Kenneth W Witwer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: 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.

OBJECTIVE: This study explored whether the non-coding RNA composition of EVs isolated from post-mortem brain tissue is related to AD pathogenesis.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)S235-S248
JournalJournal of Alzheimer's Disease
Volume99
Issue numbers2
Early online date28 Sept 2023
DOIs
Publication statusPublished - 7 May 2024
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • brain
  • ectosomes
  • exosomes
  • extracellular vesicles
  • microvesicles
  • miRNAs
  • non-coding RNAs
  • RNA sequencing
  • tRNAs

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