CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to β-amyloid fibrils

Indra Sethy Coraci, Jens Husemann, Joan W. Berman, Christine Hulette, Jennifer H. Dufour, Gabriele K. Campanella, Andrew D. Luster, Samuel C. Silverstein, Joseph B. El Khoury

Research output: Contribution to journalArticle

276 Scopus citations

Abstract

A pathological hallmark of Alzheimer's disease is the senile plaque, composed of β-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to β-amyloid fibrils and oxidized low-density lipoprotein (oxLDL)-coated surfaces. We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H2O2 secretion by macrophages adherent to oxLDL-coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H2O2 by microglia interacting with fibrillar β-amyloid is not known. Using fluorescence-activated cell sorting analysis and immunohistochemistry, we found that CD36 is expressed on human fetal microglia, and N9-immortalized mouse microglia. We also found that CD36 is expressed on microglia and on vascular endothelial cells in the brains of Alzheimer's disease patients. Bowes human melanoma cells, which normally do not express CD36, gained the ability to specifically bind to surfaces coated with fibrillar β-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar β-amyloid. Furthermore, two different monoclonal antibodies to CD36 inhibited H202 production by N9 microglia and human macrophages adherent to fibrillar β-amyloid by ∼50%. Our data identify a role for CD36 in fibrillar β-amyloid-induced H2O2 production by microglia, and imply that CD36 can mediate binding to fibrillar β-amyloid. We propose that similar to their role in the interaction of macrophages with oxLDL, class A scavenger receptors and CD36 play complimentary roles in the interactions of microglia with fibrillar β-amyloid.

Original languageEnglish (US)
Pages (from-to)101-112
Number of pages12
JournalAmerican Journal of Pathology
Volume160
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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