Journal Article

Innate immunity receptor CD36 promotes cerebral amyloid angiopathy

Zhou, Ping, Anrather, Josef, Pistick, Rose, Jamal, Sleiman El, Younkin, Steven G., Younkin, Linda, Zhou, Joan, McEwen, Bruce S., Carlson, George A., ladecola, Costantino, Park, Laibaik, Pierce, Joseph, Arreguin, Andrea

2013

Overview

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 Aß 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 Aß 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Alzheimer disease / Alzheimer's disease / Alzheimers disease / amyloid / Amyloids / Animal cognition / Animals / Arm / arterioles / Behavioral neuroscience / Biological and medical sciences / Biological Sciences / Blood brain barrier / Blood vessels / Blood Vessels - metabolism / Brain / Brain damage / CD36 Antigens - genetics / CD36 Antigens - immunology / Cerebral Amyloid Angiopathy - immunology / Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges / Cerebrovascular Circulation / cognition / Cognitive ability / Fluorescent Antibody Technique / Fundamental and applied biological sciences. Psychology / Immunity, Innate / innate immunity / Maze Learning / Mice / Mice, Transgenic / Mutation / Pericytes - immunology / Proteins / Rodents / Smooth muscle myocytes / Veins & arteries / Vertebrates: nervous system and sense organs / Zonula Occludens-1 Protein - metabolism