Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer’s disease rats
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INTRODUCTION
TREM2 is a microglial marker important in Alzheimer’s disease (AD) pathogenesis, but current methods to detect microglial TREM2 expression in vivo are limited. Circulating microglia-derived extracellular vesicles (EVs) show promise as potential biomarkers for AD and may offer insight into TREM2 activity.
METHODS
TMEM119 + /TREM2 + EVs were assessed using nanoscale flow cytometry in plasma from wildtype and APP/PS1 rats aged to 3-, 9-, and 15-months-old. Molecular and histological assays were used to assess microglia markers in rat brain tissue and a radial arm water maze task was employed to evaluate spatial working and reference memory.
RESULTS
Circulating TMEM119 + /TREM2 + EVs were increased in 15-month APP/PS1 rats and associated with severity of cognitive impairment. TREM2 brain expression varied by anatomical region, age, transgene, and assay.
DISCUSSION
Collectively, this study provides the first assessment of TMEM119 + /TREM2 + EVs as a biomarker of brain microglial expression and cognition in an AD rat model.
