CCR2

C-C chemokine receptor type 2 (CCR2 or CD192 (is_associated_with::cluster of differentiation 192) is a is_associated_with::protein that in humans is encoded by the CCR2 is_associated_with::gene. CCR2 is a is_associated_with::chemokine receptor.

Gene
This CCR2 gene is located in the is_associated_with::chemokine receptor gene cluster region. Two alternatively spliced transcript variants are expressed by the gene.

Function
This gene encodes two isoforms of a receptor for monocyte chemoattractant protein-1 (CCL2), a is_associated_with::chemokine which specifically mediates is_associated_with::monocyte is_associated_with::chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as is_associated_with::rheumatoid arthritis as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependent calcium mobilization and inhibition of is_associated_with::adenylyl cyclase.

Animal studies
CCR2 deficient mice have been shown to develop an accelerated Alzheimer's-like pathology in comparison to is_associated_with::wild type mice. This is not the first time that immune function and is_associated_with::inflammation have been linked to age-related cognitive decline (i.e. is_associated_with::dementia).

Clinical significance
In an observational study of is_associated_with::gene expression in blood is_associated_with::leukocytes in humans, Harries et al. found evidence of a relationship between expression of CCR2 and cognitive function (assessed using the is_associated_with::mini-mental state examination, MMSE). Higher CCR2 expression was associated with worse performance on the MMSE assessment of cognitive function. The same study found that CCR2 expression was also associated with cognitive decline over 9-years in a sub-analysis on inflammatory related transcripts only. Harries et al. suggest that CCR2 signaling may have a direct role in human cognition, partly because expression of CCR2 was associated with the ApoE is_associated_with::haplotype (previously associated with Alzheimer's disease), but also because CCL2 is expressed at high concentrations in is_associated_with::macrophages found in atherosclerotic plaques and in brain is_associated_with::microglia. The difference in observations between mice (CCR2 depletion causes cognitive decline) and humans (higher CCR2 associated with lower cognitive function) could be due to increased demand for macrophage activation during cognitive decline, associated with increased β-amyloid deposition (a core feature of Alzheimer's disease progression).