Longitudinal associations of serum MCP-1 with cognitive decline and psychological stress in biomarker-confirmed Alzheimer's disease: A pilot study
Abstract
Introduction Monocyte chemoattractant protein-1 (MCP-1; also known as CCL2) is a chemokine implicated in neuroinflammatory pathways that may contribute to cognitive decline in Alzheimer's disease (AD). Elevated MCP-1 is associated with glial activation, blood-brain barrier dysfunction, and immune-cell recruitment. This study assessed the longitudinal association between peripheral MCP-1 and cognitive decline in biomarker-confirmed participants across the AD continuum and explored whether psychological stress was associated with longitudinal MCP-1 changes. Methods This pilot longitudinal study included 21 amyloid-/p-tau-positive participants across the AD continuum, including six with mild cognitive impairment and 15 with AD. Participants underwent baseline and a single 1-year follow-up assessment. Global cognition was assessed using the Alzheimer's Disease Assessment Scale cognitive subscale Japanese version, and serum MCP-1 concentrations were measured using enzyme-linked immunosorbent assay. Stress response, depression, anxiety, apathy, and neuropsychiatric symptoms were assessed using validated behavioral and psychological scales. Stepwise multiple regression and partial correlation analyses were performed. Results Annual changes in peripheral MCP-1 were significantly associated with cognitive decline (β = 0.54, P = 0.005). Psychological stress, measured by the Stress Response Scale-18, was positively correlated with MCP-1 changes (r = 0.75, P = 0.003). These findings suggest that longitudinal serum MCP-1 changes may be associated with cognitive decline in the AD continuum and that psychological stress may be related to MCP-1 dynamics. Discussion MCP-1 may contribute to AD-related neuroinflammatory activity. The association between psychological stress and MCP-1 changes should be interpreted as exploratory and requires validation in larger longitudinal cohorts.