High complement levels in astrocyte-derived exosomes of Alzheimer disease

OBJECTIVE Astrocytes fulfill neuronal trophic roles normally, but are transformed in Alzheimer disease (AD) into A1-type reactive astrocytes that may destroy neurons through unknown mechanisms. METHODS To investigate astrocyte inflammatory mechanisms, astrocyte-derived exosomes (ADEs) were isolated immunochemically from plasma samples of AD patients and matched controls for enzyme-linked immunosorbent assay quantification of complement proteins. RESULTS ADE levels of C1q, C4b, C3d, factor B, factor D, Bb, C3b, and C5b-C9 terminal complement complex, but not mannose-binding lectin, normalized by the CD81 exosome marker were significantly higher for AD patients (n = 28) than age- and gender-matched controls (all p