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Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.

ABSTRACT: OBJECTIVE:To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them. METHODS:CSF ?-synuclein (?-syn), total and phosphorylated tau (t- and p-tau), and ?-amyloid 1-42 (A?42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes. RESULTS:CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF A?42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. ?-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/A?42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine imaging. CSF ?-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists. CONCLUSIONS:These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF ?-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD.

SUBMITTER: Mollenhauer B

PROVIDER: S-EPMC5679418 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.

Mollenhauer Brit B Caspell-Garcia Chelsea J CJ Coffey Christopher S CS Taylor Peggy P Shaw Leslie M LM Trojanowski John Q JQ Singleton Andy A Frasier Mark M Marek Kenneth K Galasko Douglas D

Neurology 20171013 19

<h4>Objective</h4>To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them.<h4>Methods</h4>CSF α-synuclein (α-syn), total and phosphorylated tau (t- and p-tau), and β-amyloid 1-42 (Aβ42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicent ...[more]

PMID: 29030452

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Project description:Understanding the exact pathophysiological mechanisms underlying the involvement of triggering receptor expressed on myeloid cells 2 (TREM2) related microglia activation is crucial for the development of clinical trials targeting microglia activation at different stages of Alzheimer's disease (AD). Given the contradictory findings in the literature, it is imperative to investigate the longitudinal alterations in cerebrospinal fluid (CSF) soluble TREM2 (sTREM2) levels as a marker for microglia activation, and its potential association with AD biomarkers, in order to address the current knowledge gap. In this study, we aimed to assess the longitudinal changes in CSF sTREM2 levels within the framework of the A/T/N classification system for AD biomarkers and to explore potential associations with AD pathological features, including the presence of amyloid-beta (Aβ) plaques and tau aggregates. The baseline and longitudinal (any available follow-up visit) CSF sTREM2 levels and processed tau-PET and Aβ-PET data of 1001 subjects were recruited from the ADNI database. The participants were classified into four groups based on the A/T/N framework: A+ /TN+ , A+ /TN- , A- /TN+ , and A- /TN- . Linear regression analyses were conducted to assess the relationship between CSF sTREM2 with cognitive performance, tau and Aβ-PET adjusting for age, gender, education, and APOE ε4 status. Based on our analysis there was a significant difference in baseline and rate of change of CSF sTREM2 between ATN groups. While there was no association between baseline CSF sTREM2 and cognitive performance (ADNI-mem), we found that the rate of change of CSF sTREM2 is significantly associated with cognitive performance in the entire cohort but not the ATN groups. We found that the baseline CSF sTREM2 is significantly associated with baseline tau-PET and Aβ-PET rate of change only in the A+ /TN+ group. A significant association was found between the rate of change of CSF sTREM2 and the tau- and Aβ-PET rate of change only in the A+ /TN- group. Our study suggests that the TREM2-related microglia activation and their relations with AD markers and cognitive performance vary the in presence or absence of Aβ and tau pathology. Furthermore, our findings revealed that a faster increase in the level of CSF sTREM2 might attenuate future Aβ plaque formation and tau aggregate accumulation only in the presence of Aβ pathology.

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Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.

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Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls.

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