title: Scavenger receptor A deficiency accelerates cerebrovascular amyloidosis in an animal model.
abstract: Cerebrovascular amyloidosis caused by amyloid accumulation in blood vessel walls may lead to hemorrhagic stroke and cognitive impairment. Expression of TGF-β1 under glial fibrillary acidic protein promoter in mice leads to age-related deposition of amyloid, including β-amyloid (Aβ), around cerebral blood vessels, leading to vascular pathology starting at age of 7 months. We have recently shown the important role of macrophages in clearing cerebrovascular amyloid. Scavenger receptor A (SRA) is a multi-ligand and multifunctional receptor expressed on macrophages, and it has been suggested to play a role in meditating phagocytosis of different types of antigens. We investigated the role of SRA in mediating cerebrovascular amyloid clearance. We bred TGF-β1 mice with SRA(-/-) mice and discovered that TGF-β1/SRA(-/-) mice showed cerebrovascular pathology at an earlier age (3 months) compared with TGF-β1 mice. Furthermore, SRA deficiency in macrophages led to impaired clearing of congophilic cerebrovascular amyloid from amyloid precursor protein mouse model and led to reduced phagocytosis of both soluble and insoluble Aβ in vivo as compared with macrophages from wild-type mice. Our findings demonstrate the important role of SRA in cerebrovascular amyloid pathology and suggest targeting SRA for future diagnostic and therapeutic approaches for cerebral amyloid angiopathy.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Room 424, Sherman Building, Tel Aviv 69978, Israel.
authors.forename: Veronica
authors.initials: V
authors.lastname: Lifshitz
authors.forename: Ronen
authors.initials: R
authors.lastname: Weiss
authors.forename: Hilit
authors.initials: H
authors.lastname: Levy
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D051117:Scavenger Receptors, Class A / Q000172:deficiency / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D053773:Transforming Growth Factor beta1