Plasma MCP-1 and changes on cognitive function in community-dwelling older adults

Abstract

Background Monocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition—Aβ42/40) with overall and domain-specific cognitive evolution among older adults. Methods Secondary analyses including 1097 subjects (mean age = 75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1+)) were used, as well as a dichotomy of Aβ42/40. Outcomes were measured annually over 4 years and included the following: cognitive composite z-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z-score, composite attention z-score, Free and Cued Selective Reminding Test (FCSRT - memory). Results Plasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4 years of follow-up, specifically in measures of free and cued delayed recall. MCP-1+ was associated with worse evolution in the CCS (4-year between-group difference: β = −0.14, 95%CI = −0.26, −0.02) and the CDR sum of boxes (2-year: β = 0.19, 95%CI = 0.06, 0.32). In domain-specific analyses, MCP-1+ was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ42/40, MCP-1+ was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aβ42/40× MCP-1 × time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables. Conclusions Baseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. How plasma MCP-1 interacts with Aβ42/40 to determine cognitive decline at different stages of cognitive decline/dementia should be clarified by further research. The MCP-1 association on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ42/40.

Association between Periodontal Disease and Cognitive Impairment in Adults

“…This finding has been corroborated by Takahachi et al, who reported that live P. gingivalis downregulated MCP-1 expression in cell culture [ 63 ]. Furthermore, MCP-1 levels have been shown to inconsistently affect Aβ status and deposition [ 64 ]. Although insignificant, elevated Aβ42/40 coupled with downregulation of MCP-1 had a higher magnitude of association with cognitive decline compared to elevated Aβ42/40 coupled with upregulation of MCP-1 [ 64 ].…”

“…Furthermore, MCP-1 levels have been shown to inconsistently affect Aβ status and deposition [ 64 ]. Although insignificant, elevated Aβ42/40 coupled with downregulation of MCP-1 had a higher magnitude of association with cognitive decline compared to elevated Aβ42/40 coupled with upregulation of MCP-1 [ 64 ]. Moreover, MCP-1 also plays a role in tau phosphorylation and the formation of neurofibrillary tangles [ 63 , 65 ] indicating a possible role of MCP-1 in cognitive decline and AD evolution.…”

Anti-inflammatory effects of CBD in human microglial cell line infected with HIV-1

“…MCP-1 (Monocyte chemoattractant protein-1), a beta chemokine, has been associated with various neuroinflammatory disorders, such as multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease. Notably, high Serum levels of MCP-1 levels are increased in mild cognitive impairment and mild AD 47 – 49 . Similarly, IL-8 cytokine is associated with neuroinflammatory disorders, and CBD significantly mitigated the LPS-induced NF-κB activity, IL-8, and MCP-1 in human macrophages 50 .…”

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

“…Inflammatory or chemoattractant cascades are also altered in AD. For instance, the monocyte chemoattractant protein-1 (MCP-1), during chronic inflammation, contributes to an overactivity and excessive recruitment of inflammatory cells, which leads to neuronal damage and cognitive decline [ 59 ]. Inflammation and aging are determining factors that affect innate and adaptive immune responses.…”