Dataset Information

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.

SUBMITTER: Lee WJ

PROVIDER: S-EPMC5775300 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Lee Wei-Ju WJ Liao Yi-Chu YC Wang Yen-Feng YF Lin I-Feng IF Wang Shuu-Jiun SJ Fuh Jong-Ling JL

Scientific reports 20180119 1

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 baselin ...[more]

PMID: 29352259

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Project description:Plasma-based biomarkers present a promising approach in the research and clinical practice of Alzheimer's disease as they are inexpensive, accessible and minimally invasive. In particular, prognostic biomarkers of cognitive decline may aid in planning and management of clinical care. Although recent studies have demonstrated the prognostic utility of plasma biomarkers of Alzheimer pathology or neurodegeneration, such as pTau-181 and NF-L, whether other plasma biomarkers can further improve prediction of cognitive decline is undetermined. We conducted an observational cohort study to determine the prognostic utility of plasma biomarkers in predicting progression to dementia for individuals presenting with mild cognitive impairment due to probable Alzheimer's disease. We used the Olink™ Proximity Extension Assay technology to measure the level of 460 circulating proteins in banked plasma samples of all participants. We used a discovery data set comprised 60 individuals with mild cognitive impairment (30 progressors and 30 stable) and a validation data set consisting of 21 stable and 21 progressors. We developed a machine learning model to distinguish progressors from stable and used 44 proteins with significantly different plasma levels in progressors versus stable along with age, sex, education and baseline cognition as candidate features. A model with age, education, APOE genotype, baseline cognition, plasma pTau-181 and 12 plasma Olink protein biomarker levels was able to distinguish progressors from stable with 86.7% accuracy (mean area under the curve = 0.88). In the validation data set, the model accuracy was 78.6%. The Olink proteins selected by the model included those associated with vascular injury and neuroinflammation (e.g. IL-8, IL-17A, TIMP-4, MMP7). In addition, to compare these prognostic biomarkers to those that are altered in Alzheimer's disease or other types of dementia relative to controls, we analyzed samples from 20 individuals with Alzheimer, 30 with non-Alzheimer dementias and 34 with normal cognition. The proteins NF-L and PTP-1B were significantly higher in both Alzheimer and non-Alzheimer dementias compared with cognitively normal individuals. Interestingly, the prognostic markers of decline at the mild cognitive impairment stage did not overlap with those that differed between dementia and control cases. In summary, our findings suggest that plasma biomarkers of inflammation and vascular injury are associated with cognitive decline. Developing a plasma biomarker profile could aid in prognostic deliberations and identify individuals at higher risk of dementia in clinical practice.

Project description:IntroductionBiomarkers that will reliably predict the onset of Alzheimer's disease (AD) are urgently needed. Although cerebrospinal fluid (CSF) amyloid beta 1-42 (Aβ42), total tau, and phosphorylated tau can be used to complement the clinical diagnosis of AD, amnestic mild cognitive impairment (aMCI), the prodromal phase of AD, is heterogeneous. Biomarkers should be able to determine which patients with aMCI are at greatest risk of AD. Histological studies and animal models indicate that amyloid beta 1-43 (Aβ43) aggregates early, and may play a role in the pathological process of AD. We have examined levels of CSF Aβ43 in a 2-year longitudinal study of aMCI and early AD.Materials and methodsCerebrospinal fluid was collected at baseline, and after one and 2 years from patients with AD (n = 19), and patients with aMCI (n = 42). Of these, 21 progressed to AD during the 2 years of study, whereas 21 did not. Controls (n = 32) were lumbar punctured at baseline only. CSF analyses of Aβ43, Aβ42, and total tau were carried out with ELISA.ResultsAt baseline, CSF Aβ43, CSF Aβ42 and ratios with total tau could be used to separate controls from all three patient groups. CSF Aβ43, but not Aβ42, could separate patients with aMCI who progressed to AD during the 2 years of follow-up, from those that did not. The CSF total tau/Aβ43 ratio had a slightly but significantly larger area under the receiver operating characteristic curve when compared to the CSF total tau/Aβ42 ratio. CSF Aβ43 levels, but not Aβ42 levels, decreased from baseline to 2 years in the AD group.Discussion and conclusionCSF Aβ43 was demonstrated to be significantly reduced in patients already by the time that aMCI or AD was diagnosed, compared to controls, and this change must have occurred during the preclinical period. Since our results suggested that CSF Aβ43 distinguishes between subgroups of patients with aMCI better than CSF Aβ42, it may prove to be a useful additional biomarker for identifying aMCI patients at greatest risk of AD.

Dataset Information

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

Publications

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

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