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Maternally transferred immunity may also be harnessed to target diseases associated with endogenous protein misfolding and aggregation, such as Alzheimer\u2019s disease (AD) and AD-pathology in Down syndrome (DS). While familial early-onset AD (fEOAD) is associated with autosomal dominant mutations in the\n                    <jats:italic>APP<\/jats:italic>\n                    ,\n                    <jats:italic>PSEN1,2<\/jats:italic>\n                    genes, promoting cerebral Amyloid-\u03b2 (A\u03b2) deposition, DS features a life-long overexpression of the\n                    <jats:italic>APP<\/jats:italic>\n                    and\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    genes, leading to a cognitive decline mediated by A\u03b2 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-A\u03b2 MAbs might promote the removal of early A\u03b2 accumulation in the central nervous system of human\n                    <jats:italic>APP<\/jats:italic>\n                    -expressing mice. To this end, a DNA-vaccine expressing A\u03b2\n                    <jats:sub>1-11<\/jats:sub>\n                    was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early A\u03b2 plaque formation. MAbs reduce the offspring\u2019s\u00a0cortical A\u03b2 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 Fc\u03b3R1\/Syk\/Cofilin pathway. These data suggest that maternal immunization can alleviate cognitive decline mediated by early A\u03b2 deposition, as occurs in EOAD and DS.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-01851-6","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T06:07:02Z","timestamp":1615529222000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Maternal antibodies facilitate Amyloid-\u03b2 clearance by activating Fc-receptor-Syk-mediated phagocytosis"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-6469","authenticated-orcid":false,"given":"Tomer","family":"Illouz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raneen","family":"Nicola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-5542","authenticated-orcid":false,"given":"Linoy","family":"Ben-Shushan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravit","family":"Madar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arya","family":"Biragyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"1851_CR1","doi-asserted-by":"publisher","first-page":"e1008303","DOI":"10.1371\/journal.ppat.1008303","volume":"16","author":"SN Langel","year":"2020","unstructured":"Langel, S. 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