Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 8, Pages 3089-3094Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1300021110
Keywords
cerebral blood flow; blood-brain barrier; pericytes; smooth muscle cells; tight junction
Categories
Funding
- National Institutes of Health [NS37853]
- American Heart Association [09SDG2060701]
- Alzheimer's Association
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Deposition of amyloid-beta (A beta) 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 A beta 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 A beta 1-40 and CAA. This reduced vascular amyloid deposition was associated with preservation of the A beta vascular clearance receptor LRP-1, and protection from the deleterious effects of A beta 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.
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