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

INTRODUCTIONTREM2 is a microglial marker important in Alzheimers 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. METHODSTMEM119+/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. RESULTSCirculating 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. DISCUSSIONCollectively, this study provides the first assessment of TMEM119+/TREM2+ EVs as a biomarker of brain microglial expression and cognition in an AD rat model.