The Alzheimer's disease‐associated complement receptor 1 variant confers risk by impacting glial phagocytosis

Induced pluripotent stem cell (iPSC)-derived glia from individuals expressing the Alzheimer's disease (AD) risk variant complement receptor (CR) 1*2 exhibit lower CR1 expression compared to those from donors expressing the non-risk form CR1*1. The iPSC-derived glia from individuals expressing the AD risk variant CR1*2 exhibit enhanced phagocytic activity for opsonized bacterial particles, amyloid-β aggregates and human synaptoneurosomes compared to those from donors expressing the non-risk form CR1*1. We suggest that expression of the CR1*2 variant confers risk of AD by enhancing the phagocytic capacity of glia for opsonized targets.