title: Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model.
abstract: Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein receptor that regulates cholesterol efflux from the peripheral tissues to the liver. SR-BI has been identified on astrocytes and vascular smooth muscle cells in Alzheimer's disease brain and has been shown to mediate adhesion of microglia to fibrillar amyloid-β (Aβ). Here we report that SR-BI mediates perivascular macrophage response and regulates Aβ-related pathology and cerebral amyloid angiopathy in an Alzheimer's mouse model. Reduction or deletion of SR-BI gene in heterozygous or homozygous deficient mice (SR-BI(+/-), (-/-)) resulted in a significant increase in perivascular macrophages in the brain. SR-BI deletion had no effect on apolipoprotein E or apolipoprotein AI levels in the mouse brain. Our analysis revealed increased levels of SR-BI expression in the brains of human amyloid precursor protein (Swedish, Indiana) transgenic mice (J20 line). To evaluate the role of SR-BI in Alzheimer's disease pathogenesis, we inactivated one SR-BI allele in J20 transgenic mice. SR-BI reduction in J20/SR-BI(+/-) mice enhanced fibrillar amyloid deposition and cerebral amyloid angiopathy and also exacerbated learning and memory deficits compared with J20 littermates. Immunohistochemical analysis revealed localization of SR-BI on perivascular macrophages in tight association with Aβ deposits. Our data suggest that SR-BI reduction impairs the response of perivascular macrophages to Aβ and enhances the Aβ-related phenotype and cerebral amyloid angiopathy in J20 mice. These results reveal that SR-BI, a scavenger receptor primarily involved in high-density lipoprotein cholesterol transport, plays an essential role in Alzheimer's disease and cerebral amyloid angiopathy.
authors.affiliation: Department of Cell Biology, Biomedical Research Foundation, Academy of Athens, 115 27 Athens, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Thanopoulou
authors.forename: Apostolia
authors.initials: A
authors.lastname: Fragkouli
authors.forename: Fotini
authors.initials: F
authors.lastname: Stylianopoulou
authors.forename: Spiros
authors.initials: S
authors.lastname: Georgopoulos
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism; D018384:Oxidative Stress; D010587:Phagocytosis; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051122:Scavenger Receptors, Class B / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B