Age, sex, and regional differences in scavenger receptor CD36 in the mouse brain: Potential relevance to cerebral amyloid angiopathy and Alzheimer's disease

Abstract

Scavenger receptor CD36 contributes significantly to lipid homeostasis, inflammation, and amyloid deposition, while CD36 deficiency is associated with restored cerebrovascular function in an Alzheimer's disease (AD) mouse model. Yet the distribution of CD36 has not been examined in the brain. Here, we characterized CD36 gene and protein expression in the brains of young, middle aged, aged, and elderly male and female C57BL/6J mice. Age‐related increases in CD36 mRNA expression were observed in the male hippocampus and female midbrain. Additionally, male mice had greater CD36 mRNA expression than females in the striatum, hippocampus, and midbrain. CD36 protein was primarily expressed intravascularly, and this expression differed by region, age, and sex in the mouse brain. Although male mice brains demonstrated an increase in CD36 protein with age in several cortices, basal ganglia, hippocampus, and midbrain, a decrease with age was observed in female mice in the same regions. These data suggest that distinctive age, region, and sex expression of CD36 in the brain may contribute to Aβ deposition and neuroinflammation in AD.

A Single-cell and Spatial RNA-seq Database for Alzheimer’s Disease (ssREAD)

“…In AD, the dysregulation of scavenger receptor activity has been implicated in the clearance of Aβ plaques, which are one of the hallmark pathological features of the disease 34 . Previous studies have reported sex differences in scavenger receptor expression in the context of AD 35 . Additionally, we observed differences in GSEA enrichment of neurogenesis pathways in Microglia under AD conditions.…”

Membrane phospholipids activate the inflammatory response in macrophages by various mechanisms

“…Interestingly, food deprivation was found to inhibit hepatic CD36 expression in a female‐specific manner, whereas food deprivation resulted in an increase of CD36 expression in skeletal muscle, demonstrating a tissue‐specific regulation of CD36 26 . In that regard, different expressions of CD36 mRNA were found in several parts of male and female C57BL/6J mice, with higher expression of CD36 mRNA in the striatum, hippocampus, and midbrain of male animals 27 . CD36 is an 88 kDa cell surface glycoprotein that belongs to class B of scavenger receptors, which have been shown to localize within lipid rafts 28 .…”

“…26 In that regard, different expressions of CD36 mRNA were found in several parts of male and female C57BL/6J mice, with higher expression of CD36 mRNA in the striatum, hippocampus, and midbrain of male animals. 27 CD36 is an 88 kDa surface glycoprotein that belongs to class B of receptors, which have been shown to localize within lipid rafts. 28 CD36 recognizes a variety of ligands, including lipoproteins from the bacterial wall and mammalian cells, microparticles, and apoptotic cells.…”

β‐Carotene Bioavailability and Conversion Efficiency Are Significantly Affected by Sex in Rats

“…Indeed, this hypothesis agrees with the lower retinolemia in females and could be due to either a lower hepatic expression of its transporter protein, i.e., RBP4, [37] leading to a lower plasma concentration of VA, or to a difference in expression of Cd36 between males and females. [45] Indeed, it has been shown that this protein plays a role in the mobilization of hepatic VA stores, since Cd36 -/mice accumulated higher hepatic VA stores than wild type mice. [46] The last parameter of hepatic metabolism of VA that was affected by the sex of animals was the relative proportions of each retinyl ester species.…”