CD36 in Alzheimer’s Disease: An Overview of Molecular Mechanisms and Therapeutic Targeting

• Published in: Neuroscience Vol. 453; pp. 301 - 311
• Main Authors: Dobri, Ana-Maria, Dudău, Maria, Enciu, Ana-Maria, Hinescu, Mihail Eugen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.01.2021
• Subjects: Alzheimer Disease - drug therapy; Alzheimer’s disease; Amyloid beta-Peptides - metabolism; amyloid peptide; Animals; CD36; CD36 Antigens; Endothelial Cells - metabolism; fatty acids; Humans; Microglia - metabolism; neuroinflammation; SR-B2; APP; AD; Alzheimer’s disease; fatty acids; CNS; SR-B2; LCFA; MCI; amyloid peptide; neuroinflammation; GPIV; FAT; SNPs; CD36
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2020.11.003

•CD 36 is a microglial scavenger receptor, involved in Aβ clearance.•In AD brain, pro-inflammatory microglia downregulates CD36 expression.•Pharmacologic manipulation of CD36 improved Aβ clearance in AD mouse models.•There are insufficient clinical data of CD36 involvement in AD. CD36 is a membrane protein with wide distribution in the human body, is enriched in the monocyte-macrophage system and endothelial cells, and is involved in the cellular uptake of long chain fatty acids (LCFA) and oxidized low-density lipoproteins. It is also a scavenger receptor, binding hydrophobic amyloid fibrils found in the Alzheimer’s disease (AD) brain. In neurobiology research, it has been mostly studied in relationship with chronic ischemia and stroke, but it was also related to amyloid clearance by microglial phagocytosis. In AD animal models, amyloid binding to CD36 has been consistently correlated with a pro-inflammatory response. Therapeutic approaches have two main focuses: CD36 blockade with monoclonal antibodies or small molecules, which is beneficial in terms of the inflammatory milieu, and upregulation of CD36 for increased amyloid clearance. The balance of the two approaches, centered on microglia, is poorly understood. Furthermore, CD36 evaluation in AD clinical studies is still at a very early stage and there is a gap in the knowledge regarding the impact of LCFA on AD progression and CD36 expression and genetic phenotype. This review summarizes the role played by CD36 in the pathogenic amyloid cascade and explore the translatability of preclinical data towards clinical research.