Maternal antibodies facilitate Amyloid-β clearance by activating Fc-receptor-Syk-mediated phagocytosis

Down Syndrome (DS) features a life-long overexpression of the APP and DYRK1A genes, leading to a cognitive decline mediated by Amyloid-{beta} (A{beta}) overproduction and tau hyper-phosphorylation. As DS can be diagnosed in utero, maternally transferred anti-A{beta} antibodies might promote removal of early accumulation of A{beta} from the CNS. A DNA-vaccine expressing A{beta}1-11 was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early A{beta} plaque formation, similar to individuals with DS. Maternal A{beta}-specific antibodies provided transgenic offspring with passive immunization against A{beta} via the placental and subsequently lactation. Maternal antibodies reduced cortical A{beta} levels 4 months after antibodies were undetectable, along with alleviating short-term memory deficits and activation of the Fc{gamma}R1/Syk/Cofilin pathway in microglia. Sera from immunized dams facilitated A{beta} clearance by microglia in a Syk-dependent manner. These data suggest that maternal anti-A{beta} immunization is a potential strategy to alleviate cognitive decline in individuals with DS.