A report on ASIC2021: a conference on extracellular vesicle communication mechanisms.

AD. His group generated human induced pluripotent stem cells (hiPSCs) and differentiated them into neuronal, astrocytic, oligodendrocytic, and microglial cell types. Proteomic profiles of EVs from these differentiated iPSC cells contained cell-type specific markers: excitatory neurons (ATP1A3, NCAM1); astrocytes (LRP1, ITGA6); microglia-like cells (ITGAM, CD300A); and oligodendrocyte-like cells (LAMP2, FTH1). There were also 16 pan-EV marker candidates, including integrins and annexins. Cell type-specific EV proteins could also be found when comparing their data to CSF EV proteomic datasets, which also held true for brain-derived EVs. Correlation networks and pathway analyses identified proteins in each cell subset EVs with co-expression in AD. It was shown that astrocyte-specific EV (ADEV) markers were most significantly associated with AD pathology and cognitive impairment, thereby underscoring the role of ADEVs in AD progression. The hub protein from this module, integrin- β 1 (ITGB1), was elevated in ADEVs purified from total brain-derived EVs and associated with brain A β 42 and tau load in independent cohorts. From this, it was found that astrocytes are likely in an activated state due to IL1B, and astrocytic AD EVs are enriched in ITGB1. This correlated with A β 42 and phosphoTau, and these EVs enhance neuronal uptake via integrin signaling. Thus, this study provides a featured framework and rich resource for analyses of EV functions in neurodegenerative diseases in a cell type-specific manner.