Similar to microglia, we mapped homeostatic (GPC5, LSAMP, TRPM3) and composite activation signatures (B2M, CRYAB, VIM, GFAP, AQP4, APOE, ITM2B, CD81, FTL) to early-disease-enriched and control-enriched astrocyte clusters across neurodegenerative diseases. Here, GPC5 is linked to neurodegenerative disease.