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- Donker Kaat, Laura, et al.
(author)
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Serum neurofilament light chain in progressive supranuclear palsy.
- 2018
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In: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 56
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Journal article (peer-reviewed)abstract
- Neurofilament light chain (NfL) is a promising biomarker in neurodegenerative diseases. Elevated NfL levels in CSF and blood have been observed in a growing number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease. We studied serum NfL levels in patients with progressive supranuclear palsy (PSP) in relation to disease severity and survival.Serum NfL levels were determined cross-sectionally in a retrospective cohort of 131 patients with PSP and 95 healthy controls. Detailed clinical examination was performed and disease severity was assessed by several rating scales.We found that serum NfL levels in PSP were twice as high as those in controls, and that NfL levels correlated with worse functional, motor and cognitive functioning. During follow-up, 119 PSP patients had died, and higher NfL levels were associated with a shorter survival.This study provides evidence that serum NfL is a relevant and promising biomarker in PSP for disease severity, and may be used as a prognostic tool to predict survival in clinical practice.
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| 2. |
- Førland, Marthe Gurine, et al.
(author)
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Evolution of cerebrospinal fluid total α-synuclein in Parkinson's disease.
- 2018
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In: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 49, s. 4-8
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) total α-synuclein is considered a potential biomarker for Parkinson's disease (PD), but little is known about the evolution of this marker during the course of the disease. Our objective was to investigate whether CSF total α-synuclein concentrations change over time and are associated with motor and cognitive function in PD.CSF total α-synuclein concentrations were quantified in 56 longitudinally followed PD patients, 27 of whom provided CSF repeatedly 2 and/or 4 years later. Another 18 subjects were included as controls. The samples were analyzed using two independent, validated ELISA methods: our recently developed and validated in-house ELISA and a commercial kit from BioLegend.CSF total α-synuclein levels did not distinguish PD patients from controls, displayed no substantial changes during a period of up to 4 years, and did not predict subsequent motor or cognitive decline. These findings were consistent for both analytical methods.Our findings do not support the clinical utility of total α-synuclein as a single diagnostic or prognostic biomarker in PD.
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| 3. |
- Magdalinou, N. K., et al.
(author)
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Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics
- 2017
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In: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 37, s. 65-71
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Journal article (peer-reviewed)abstract
- Introduction: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than a-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. Objectives: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls. Methods: CSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set. Results: 79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism. Conclusion: Using an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as candidate biomarkers in parkinsonism. (C) 2017 Published by Elsevier Ltd.
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