Increased circulating TREM2+ microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

Sarah J Myers1, Manoj Reddy Medapati1, Brian L Allman1

  • 1Vulnerable Brain Lab, Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Insights

Researchers identified TREM2-expressing microglial extracellular vesicles (EVs) in rat plasma. Increased levels of these EVs correlated with cognitive decline in an Alzheimer

Area of Science:

  • Neuroscience
  • Biomarkers
  • Alzheimer's Disease Research

Background:

  • TREM2 is a key microglial marker implicated in Alzheimer's disease (AD) pathogenesis.
  • Detecting TREM2 expression *in vivo* is challenging, limiting understanding of its role.
  • Extracellular vesicles (EVs), particularly microglial EVs (MEVs), are emerging as promising biomarkers.

Purpose of the Study:

  • To investigate plasma-derived TREM2+ MEVs as peripheral indicators of brain microglial TREM2 activity.
  • To assess the relationship between TREM2+ MEVs and cognitive function in a rat model of aging and AD.
  • To establish TMEM119+/TREM2+ EVs as a potential peripheral biomarker for AD-related microglial changes.

Main Methods:

  • Fluorescent labeling and nanoscale flow cytometry of TMEM119+/TREM2+ EVs in rat plasma.
  • Analysis of plasma from wildtype and APP/PS1 rats at 3, 9, and 15 months of age.
  • Assessment of brain microglial markers, TREM2 expression, and spatial memory using radial arm water maze.

Main Results:

  • TMEM119+/TREM2+ EVs were successfully detected in systemic circulation.
  • Elevated levels of TMEM119+/TREM2+ EVs were observed in aged APP/PS1 rats (15 months).
  • A modest association was found between TMEM119+/TREM2+ EV levels and cognitive impairment severity.

Conclusions:

  • Plasma-derived TMEM119+/TREM2+ EVs can serve as a peripheral indicator of brain microglial activity.
  • These EVs show potential as a non-invasive biomarker for cognitive impairment in aging and AD.
  • This study provides a novel method for assessing microglial function peripherally in AD models.