| First Author | Illouz T | Year | 2021 |
| Journal | Commun Biol | Volume | 4 |
| Issue | 1 | Pages | 329 |
| PubMed ID | 33712740 | Mgi Jnum | J:348197 |
| Mgi Id | MGI:6714983 | Doi | 10.1038/s42003-021-01851-6 |
| Citation | Illouz T, et al. (2021) Maternal antibodies facilitate Amyloid-beta clearance by activating Fc-receptor-Syk-mediated phagocytosis. Commun Biol 4(1):329 |
| abstractText | Maternal antibodies (MAbs) protect against infections in immunologically-immature neonates. Maternally transferred immunity may also be harnessed to target diseases associated with endogenous protein misfolding and aggregation, such as Alzheimer's disease (AD) and AD-pathology in Down syndrome (DS). While familial early-onset AD (fEOAD) is associated with autosomal dominant mutations in the APP, PSEN1,2 genes, promoting cerebral Amyloid-beta (Abeta) deposition, DS features a life-long overexpression of the APP and DYRK1A genes, leading to a cognitive decline mediated by Abeta overproduction and tau hyperphosphorylation. Although no prenatal screening for fEOAD-related mutations is in clinical practice, DS can be diagnosed in utero. We hypothesized that anti-Abeta MAbs might promote the removal of early Abeta accumulation in the central nervous system of human APP-expressing mice. To this end, a DNA-vaccine expressing Abeta1-11 was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early Abeta plaque formation. MAbs reduce the offspring's cortical Abeta levels 4 months after antibodies were undetectable, along with alleviating short-term memory deficits. MAbs elicit a long-term shift in microglial phenotype in a mechanism involving activation of the FcgammaR1/Syk/Cofilin pathway. These data suggest that maternal immunization can alleviate cognitive decline mediated by early Abeta deposition, as occurs in EOAD and DS. |
