Biomarker and therapeutic potential of peripheral extracellular vesicles in Alzheimer's disease

Extracellular vesicles (EVs) are cell-derived nanoparticles with an important role in intercellular communication, even across brain barriers. The bidirectional brain-barrier crossing capacity of EVs is supported by research identifying neuronal markers in peripheral EVs, as well as the brain delivery of peripherally administered EVs. In addition, EVs are reflective of their cellular origin, underlining their biomarker and therapeutic potential when released by diseased and regenerative cells, respectively. Both characteristics are of interest in Alzheimer's disease (AD) where the current biomarker profile is solely based on brain-centered readouts and effective therapeutic options are lacking. In this review, we elaborate on the role of peripheral EVs in AD. We focus on bulk EVs and specific EV subpopulations including bacterial EVs (bEVs) and neuronal-derived EVs (nEVs), which have mainly been studied from a biomarker perspective. Furthermore, we highlight the therapeutic potential of peripherally administered EVs whereby research has centered around stem cell derived EVs.