C3 in postmortem tissue samples. In demyelinating lesions of MS, C3-positive astrocytes were typically closely associated with CD68 positive activated microglia/macrophages (Fig. 5; Extended Data Fig. 11). In human AD, nearly 60% of GFAP positive astrocytes in the prefrontal cortex were positive for C3, suggesting that A1 activated astrocytes make up a large proportion of astrocytes in AD in CNS regions affected by neurodegeneration, and may thus be integral for disease initiation and progression. In addition to C3, reactive astrocytes in these diseases were also immunoreactive for several other A1 specific markers (Extended Data Fig. 11). These findings demonstrate that A1-like reactive astrocytes are present in most major neurodegenerative diseases, where they are likely to help to drive neurodegeneration.
