Plasma MCP-1 and Cognitive Decline in Patients with Alzheimer's Disease and Mild Cognitive Impairment: A Two-year Follow-up Study

Abstract

Monocyte chemoattractant protein-1 (MCP-1, also known as chemokine CCL2) is a vital chemokine that mediates inflammation in Alzheimer's disease (AD). We analyzed the associations between the baseline plasma MCP-1 level, longitudinal cognitive changes, and genetic effects of CCL2 rs1024611 and its receptor, CC-chemokine receptor 2 (CCR2) rs1799864, in AD. In total, 310 AD patients and 66 mild cognitive impairment (MCI) patients were followed for 2 years, and 120 controls were recruited at baseline for comparison. After adjusting for covariates using one-way analysis of covariance, AD patients had higher plasma MCP-1 levels compared with MCI patients and controls, and severe AD patients had the highest levels. After adjusting for covariates using generalized estimating equation analysis, the results showed that the baseline MCP-1 level was significantly correlated with changes in the two-year Mini-Mental Status Examination (p = 0.046). The A allele of CCR2 rs1799864 was associated with a higher MCP-1 level in AD and MCI patients. In conclusion, plasma MCP-1 might reflect the risk and disease course of AD. A higher plasma MCP-1 level is associated with greater severity and faster cognitive decline. Additionally, the CCR2 polymorphism may play a role in the regulation of MCP-1/CCR2 signaling in AD.

Figure 1

The effects of the CCL2 and CCR2 genotypes on the plasma MCP-1 levels. Plasma MCP-1 levels were similar among the different genotypes of CCL2 rs1024611 in all groups of participants. However, the A allele of CCR2 rs1799864 appeared to exert an additive effect on the plasma MCP-1 levels, with the highest levels observed in the AA genotype, followed by the AG genotype, and the lowest levels were observed in the GG genotype. The p-value was calculated by multiple linear regression models while adjusting for age, sex, APOE ε4 carrier status, and CCI. The error bars indicate standard deviation. Abbreviations: CCL2, Chemokine ligand 2; CCR2, CC-chemokine receptor 2; MCP-1, Monocyte chemotactic protein-1; APOE, apolipoprotein E; CCI, Charlson comorbidity index.