Innate immunity receptor CD36 promotes cerebral amyloid angiopathy

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

Research output: Contribution to journalArticle

75 Scopus citations

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 effectswere reflected bymarked 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.

Original languageEnglish (US)
Pages (from-to)3089-3094
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number8
DOIs
StatePublished - Feb 19 2013

Keywords

  • Blood-brain barrier
  • Cerebral blood flow
  • Pericytes
  • Smooth muscle cells
  • Tight junction

ASJC Scopus subject areas

  • General

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  • Cite this

    Park, L., Zhou, J., Zhou, P., Pistick, R., Jamal, S. E., Younkin, L., Pierce, J., Arreguin, A., Anrather, J., Younkin, S. G., Carlsonb, G. A., McEwen, B. S., & Iadecola, C. (2013). Innate immunity receptor CD36 promotes cerebral amyloid angiopathy. Proceedings of the National Academy of Sciences of the United States of America, 110(8), 3089-3094. https://doi.org/10.1073/pnas.1300021110