Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies

Llorens, Franc; Schmitz, Matthias; Varges, Daniela; Kruse, Niels; Gotzmann, Nadine; Gmitterová, Karin; Mollenhauer, Brit; Zerr, Inga

doi:10.1007/s00415-016-8259-0

Cited by 44 publications

(38 citation statements)

References 45 publications

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“…This was further substantiated when we found that in a bilateral comparison, the combination of o‐α‐syn and tau optimally discriminates DLB from AD. Taken together with the results of previous studies, our observations underline the potential of combining α‐syn species with other biomarkers like Aβ 1‐42 , tau, and p‐tau to improve the differential diagnosis of DLB. Other, yet to be discovered potential biomarker candidates or posttranslationally modified α‐syn species, may also be useful for this purpose.…”

Section: Discussionsupporting

confidence: 81%

α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

et al. 2018

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Background: The 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. Methods: We 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. Results: CSF 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‐β 1‐42 . The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid‐β 1‐42 , 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. Conclusions: CSF 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.

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Section: Discussionsupporting

confidence: 81%

α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

et al. 2018

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“…Consistent with our hypothesis, the serum levels of sLAG‐3 in PD patients increased when compared with NC in the present study. We also found that serum sLAG‐3 in ET is lower than in PD and similar to levels in NC, in agreement with previous findings that α‐syn level in both cerebrospinal fluid (CSF) and peripheral blood is similar in ET and NC . However, the risk of developing PD in ET is higher than in healthy people .…”

Section: Discussionsupporting

confidence: 91%

Serum soluble lymphocyte activation gene‐3 as a diagnostic biomarker in Parkinson's disease: A pilot multicenter study

Cui

Liu

et al. 2018

Movement Disorders

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Objective Lymphocyte activation gene‐3 (LAG‐3) could mediate pathological α‐synuclein transmission in neurodegeneration and may be involved in the pathogenesis of Parkinson's disease (PD). The aim of the present study was to explore soluble LAG‐3 (sLAG‐3) as a potential diagnostic biomarker for PD. Methods Serum sLAG‐3 concentrations were measured by a quantitative ELISA for patients with PD, essential tremor (ET) and age‐ and sex‐matched controls. The relationships between sLAG‐3 and clinical phenotype were assessed via correlation analysis and logistic regression. Results Serum sLAG‐3 levels in patients with PD were significantly higher than those in ET patients and age‐ and sex‐matched controls. The area under the curve of serum sLAG‐3 in differentiating PD from age‐ and sex‐matched controls was 0.82. Serum sLAG‐3 was associated with non‐motor symptoms and excessive daytime sleep. Conclusion sLAG‐3 is a candidate novel biomarker for PD. © 2018 International Parkinson and Movement Disorder Society

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“…Tau and α‐syn interact and promote each other's aggregation, and co‐occurrence of tau and t‐α‐syn inclusions are frequent in PD, DLB and AD . A positive correlation was found between t‐α‐syn and t‐tau which is in line with previous studies . Two previous studies have reported an improved diagnostic performance using the t‐tau/t‐α‐syn ratio in distinguishing PD from controls .…”

Section: Discussionsupporting

confidence: 90%

The value of cerebrospinal fluid α‐synuclein and the tau/α‐synuclein ratio for diagnosis of neurodegenerative disorders with Lewy pathology

Førland

Tysnes

Aarsland

et al. 2019

Euro J of Neurology

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Background and purpose Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are three of the most common neurodegenerative disorders. Up to 20% of these patients have the wrong diagnosis, due to overlapping symptoms and shared pathologies. A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking. Using well‐defined, community‐based cohorts and validated analytical methods, the diagnostic value of CSF total‐α‐synuclein (t‐α‐syn) alone and in combination with total tau (t‐tau) in newly diagnosed patients with PD, DLB and AD was determined. Methods Cerebrospinal fluid concentrations of t‐α‐syn were assessed using our validated in‐house enzyme‐linked immunosorbent assay in 78 PD patients, 20 AD patients, 19 DLB patients and 32 controls. t‐tau was measured using a commercial assay. Diagnostic performance was assessed by receiver operating characteristic curve analysis. Results Compared to controls (mean 517 pg/ml), significantly lower levels of CSF t‐α‐syn in patients with PD (434 pg/ml, 16% reduction, P = 0.036), DLB (398 pg/ml, 23% reduction, P = 0.009) and AD (383 pg/ml, 26% reduction, P = 0.014) were found. t‐α‐syn levels did not differ significantly between PD, DLB and AD. The t‐tau/t‐α‐syn ratio showed an improved performance compared to the single markers. Conclusion This is the first study to compare patients with PD, DLB and AD at the time of diagnosis. It was found that t‐α‐syn can contribute as a teammate with tau in a CSF biomarker panel for PD and DLB, and strengthen the existing biomarker panel for AD.

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Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies

Cited by 44 publications

References 45 publications

α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

α‐Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

Serum soluble lymphocyte activation gene‐3 as a diagnostic biomarker in Parkinson's disease: A pilot multicenter study

The value of cerebrospinal fluid α‐synuclein and the tau/α‐synuclein ratio for diagnosis of neurodegenerative disorders with Lewy pathology

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