Dataset Information

Cerebrospinal Fluid ?-Synuclein Species in Cognitive and Movements Disorders.

ABSTRACT: Total CSF ?-synuclein (t-?-syn), phosphorylated ?-syn (pS129-?-syn) and ?-syn oligomers (o-?-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of ?-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF ?-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson's disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer's disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-?-syn/?-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower ?-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-?-syn levels (p = 0.002; cut-off value: ?865 pg/mL; sensitivity: 95%, specificity: 69%) and higher pS129-/t-?-syn ratios (p = 0.020; cut-off value: ?0.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant ?-syn species alterations in non-synucleinopathies.

SUBMITTER: Constantinides VC

PROVIDER: S-EPMC7830324 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cerebrospinal Fluid <i>α</i>-Synuclein Species in Cognitive and Movements Disorders.

Constantinides Vasilios C VC Majbour Nour K NK Paraskevas George P GP Abdi Ilham I Safieh-Garabedian Bared B Stefanis Leonidas L El-Agnaf Omar M OM Kapaki Elisabeth E

Brain sciences 20210117 1

Total CSF α-synuclein (t-α-syn), phosphorylated α-syn (pS129-α-syn) and α-syn oligomers (o-α-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of α-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF α-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 pati ...[more]

PMID: 33477387

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Project description:BackgroundThe objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.MethodsWe applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers.ResultsCSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β1-42 . The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid-β1-42 , tau, total α-synuclein, oligomeric α-synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α-synuclein resulted in an AUC of 0.83. CSF α-synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD.ConclusionsCSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Cerebrospinal Fluid ?-Synuclein Species in Cognitive and Movements Disorders.

Publications

Cerebrospinal Fluid <i>α</i>-Synuclein Species in Cognitive and Movements Disorders.

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