Scavenger receptor CD36 is essential for the cerebrovascular oxidative stress and neurovascular dysfunction induced by amyloid-β

• DOI: 10.1073/pnas.1015413108
• Publication Date: 2011-03-08T12:01:21Z
• Authors: Laibaik Park; Gang Wang; Ping Zhou; Joan Zhou; Rose Pitstick; Mary Lou Previti; Linda Younkin; Steven G. Younkin; William E. Van No...; Sunghee Cho; Josef Anrather; George A. Carlson; Costantino Iadecola
• Keywords: CD36; Vascular dementia

Increasing evidence indicates that cerebrovascular dysfunction plays a pathogenic role in Alzheimer's dementia (AD). Amyloid-β (Aβ), peptide central to the pathogenesis of AD, has profound vascular effects mediated, for most part, by reactive oxygen species produced enzyme NADPH oxidase. The mechanisms linking Aβ oxidase-dependent oxidative stress have not been identified, however. We report scavenger receptor CD36, membrane glycoprotein binds Aβ, is essential and neurovascular induced 1–40 . Thus, topical application onto somatosensory cortex attenuates increase cerebral blood flow elicited neural activity or endothelium-dependent vasodilators WT mice but CD36-null (CD36 0/0 ). infusion into arteries are observed pretreated with CD36 blocking antibodies mice. Furthermore, deficiency prevents transgenic overexpressing Swedish mutation amyloid precursor protein Tg2576 despite elevated levels brain also required exogenous These observations establish as key link between underlying suggest potential therapeutical target counteract associated Aβ.