In an observational study of gene expression in blood leukocytes in humans, Harries et al. found evidence of a relationship between expression of CCR2 and cognitive function (assessed using the 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 ApoEhaplotype (previously associated with Alzheimer's disease), but also because CCL2 is expressed at high concentrations in macrophages found in atherosclerotic plaques and in brain 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).
^ abEl Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (April 2007). "Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease". Nat. Med.13 (4): 432–8. doi:10.1038/nm1555. PMID17351623.
Yamagami S, Tokuda Y, Ishii K, et al. (1994). "cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor". Biochem. Biophys. Res. Commun.202 (2): 1156–62. doi:10.1006/bbrc.1994.2049. PMID8048929.
Combadiere C, Ahuja SK, Van Damme J, et al. (1996). "Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B". J. Biol. Chem.270 (50): 29671–5. doi:10.1074/jbc.270.50.29671. PMID8530354.
Samson M, Soularue P, Vassart G, Parmentier M (1997). "The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3". Genomics36 (3): 522–6. doi:10.1006/geno.1996.0498. PMID8884276.
Wong LM, Myers SJ, Tsou CL, et al. (1997). "Organization and differential expression of the human monocyte chemoattractant protein 1 receptor gene. Evidence for the role of the carboxyl-terminal tail in receptor trafficking". J. Biol. Chem.272 (2): 1038–45. doi:10.1074/jbc.272.2.1038. PMID8995400.
Polentarutti N, Allavena P, Bianchi G, et al. (1997). "IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences". J. Immunol.158 (6): 2689–94. PMID9058802.
Gong X, Gong W, Kuhns DB, et al. (1997). "Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors". J. Biol. Chem.272 (18): 11682–5. doi:10.1074/jbc.272.18.11682. PMID9115216.
Daugherty BL, Springer MS (1997). "The beta-chemokine receptor genes CCR1 (CMKBR1), CCR2 (CMKBR2), and CCR3 (CMKBR3) cluster within 285 kb on human chromosome 3p21". Genomics41 (2): 294–5. doi:10.1006/geno.1997.4626. PMID9143512.
Berkhout TA, Sarau HM, Moores K, et al. (1997). "Cloning, in vitro expression, and functional characterization of a novel human CC chemokine of the monocyte chemotactic protein (MCP) family (MCP-4) that binds and signals through the CC chemokine receptor 2B". J. Biol. Chem.272 (26): 16404–13. doi:10.1074/jbc.272.26.16404. PMID9195948.
Smith MW, Dean M, Carrington M, et al. (1997). "Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study". Science277 (5328): 959–65. doi:10.1126/science.277.5328.959. PMID9252328.
Monteclaro FS, Charo IF (1997). "The amino-terminal domain of CCR2 is both necessary and sufficient for high affinity binding of monocyte chemoattractant protein 1. Receptor activation by a pseudo-tethered ligand". J. Biol. Chem.272 (37): 23186–90. doi:10.1074/jbc.272.37.23186. PMID9287323.
Frade JM, Mellado M, del Real G, et al. (1998). "Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells". J. Immunol.159 (11): 5576–84. PMID9548499.
Mummidi S, Ahuja SS, Gonzalez E, et al. (1999). "Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression". Nat. Med.4 (7): 786–93. doi:10.1038/nm0798-786. PMID9662369.