title: Innate immunity receptor CD36 promotes cerebral amyloid angiopathy.
abstract: Deposition of amyloid-β (Aβ) in cerebral arteries, known as cerebral amyloid angiopathy (CAA), occurs both in the setting of Alzheimer's disease and independent of it, and can cause cerebrovascular insufficiency and cognitive deficits. The mechanisms leading to CAA have not been established, and no therapeutic targets have been identified. We investigated the role of CD36, an innate immunity receptor involved in Aβ trafficking, in the neurovascular dysfunction, cognitive deficits, and amyloid accumulation that occurs in mice expressing the Swedish mutation of the amyloid precursor protein (Tg2576). We found that Tg2576 mice lacking CD36 have a selective reduction in Aβ1-40 and CAA. This reduced vascular amyloid deposition was associated with preservation of the Aβ vascular clearance receptor LRP-1, and protection from the deleterious effects of Aβ on cerebral arterioles. These beneficial vascular effects were reflected by marked improvements in neurovascular regulation and cognitive performance. Our data suggest that CD36 promotes vascular amyloid deposition and the resulting cerebrovascular damage, leading to neurovascular dysfunction and cognitive deficits. These findings identify a previously unrecognized role of CD36 in the mechanisms of vascular amyloid deposition, and suggest that this scavenger receptor is a putative therapeutic target for CAA and related conditions.
authors: Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA.
authors: Laibaik
authors: L
authors: Park
authors: Joan
authors: J
authors: Zhou
authors: Ping
authors: P
authors: Zhou
authors: Rose
authors: R
authors: Pistick
authors: Sleiman
authors: S
authors: El Jamal
authors: Linda
authors: L
authors: Younkin
authors: Joseph
authors: J
authors: Pierce
authors: Andrea
authors: A
authors: Arreguin
authors: Josef
authors: J
authors: Anrather
authors: Steven G
authors: SG
authors: Younkin
authors: George A
authors: GA
authors: Carlson
authors: Bruce S
authors: BS
authors: McEwen
authors: Costantino
authors: C
authors: Iadecola
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology*; D016657:Cerebral Amyloid Angiopathy / Q000276:immunology*; D002560:Cerebrovascular Circulation; D005455:Fluorescent Antibody Technique; D007113:Immunity, Innate; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D020286:Pericytes / Q000276:immunology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein
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