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
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A pathological hallmark of Alzheimer's disease is the senile plaque, composed of beta-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to beta-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 H(2)O(2) secretion by macrophages adherent to oxLDL-coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H(2)O(2) by microglia interacting with fibrillar beta-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 beta-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar beta-amyloid. Furthermore, two different monoclonal antibodies to CD36 inhibited H(2)O(2) production by N9 microglia and human macrophages adherent to fibrillar beta-amyloid by approximately 50%. Our data identify a role for CD36 in fibrillar beta-amyloid-induced H(2)O(2) production by microglia, and imply that CD36 can mediate binding to fibrillar beta-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 beta-amyloid.
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PCSK9 interaction with CD36 may elicit pro-oxidative events; CD36 is expressed on microglia and vascular ECs in AD brain where it promotes fibrillar Aβ-mediated H2O2 production.
“Moreover, pro-oxidative events might be elicited by PCSK9 thanks to its interaction with CD36, which is expressed on microglia cells and on vascular ECs in the brain of AD patients where it promotes fibrillar Aβ-mediated H2O2 production [119].”
From The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer’s Disease: A Possible Target for the Disease Treatment (2024) · cites this paper as [119]
Microglia-Aβ interactions lead to early synapse loss, production of ROS and RNS, NLRP3 inflammasome activation, and proinflammatory cytokines and TNF.
“Microglia–Aβ interactions lead to early synapse loss39, production of neurotoxic reactive oxygen and nitrogen species (ROS and RNS), NLRP3 inflammasome activation, and production of proinflammatory cytokines and TNF27,40–42.”
From Microglia in neurodegeneration (2018) · cites this paper as [40]
CD36 (SR-B2) is a microglial Aβ receptor; it complexes with TLR-4 and TLR-6, causing cytokine, chemokine, and ROS production, microglial migration, inflammasome activation, and neurotoxicity.
“SR-B2 (also called CD36) is also a microglial Aβ receptor that forms a complex with TLR-4 and TLR-6, leading to cytokine, chemokine, and ROS production, as well as microglial migration, inflammasome activation, and neurotoxicity27,40.”
From Microglia in neurodegeneration (2018) · cites this paper as [40]
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- Authors
- Coraci, I. S., Husemann, J., Berman, J. W., Hulette, C., Dufour, J. H., Campanella, G. K., Luster, A. D., Silverstein, S. C., & El Khoury, J. B.
- Affiliations
- Columbia University Irving Medical Center (US)
- Albert Einstein College of Medicine (US)
- Duke University (US)
- Harvard University (US)
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 160
- Issue
- 1
- Pages
- 101-112
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1867121
- OpenAlex
- W2096519700
- Cited by
- 398
- References
- 56
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 13 · 2023: 10 · 2022: 16 · 2021: 18 · 2020: 29 · 2019: 17 · 2018: 10 · 2017: 16 · 2016: 16 · 2015: 18 · 2014: 29 · 2013: 18 · 2012: 33
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke
- National Heart, Lung, and Blood Institute (PO1-AG02219, P50-AG05138)
- Alzheimer's Association (R37-AI 20516)
- National Institute of Allergy and Infectious Diseases (HL43310)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- CD36, scavenger receptor class B, microglia, Alzheimer's disease, amyloid-beta fibrils, reactive oxygen species, hydrogen peroxide production, amyloid plaques, vascular endothelial cells, monoclonal antibody inhibition
- MeSH terms
- Alzheimer Disease, Animals, Antibodies, Brain, Cell Adhesion, Cell Line, Cell Line, Transformed, Fetus, Humans, Macrophages, Membrane Proteins, Peptide Fragments, Peroxides, Phagocytes, Receptors, Immunologic, Amyloid beta-Peptides, Reactive Oxygen Species, Microglia, Receptors, Lipoprotein, CD36 Antigens, Receptors, Scavenger, Scavenger Receptors, Class A, Scavenger Receptors, Class B, Mice, Rats
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