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

Several studies have addressed the utility of cerebrospinal (CSF) [alpha]-synuclein levels as a potential biomarker of [alpha]-synuclein aggregation disorders. However, its relevance in the differential diagnostic context of neurodegenerative and movement disorders is still a contentious subject. He...

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Bibliographic Details
Published in:Journal of neurology 2016-11, Vol.263 (11), p.2271
Main Authors: Llorens, Franc, Schmitz, Matthias, Varges, Daniela, Kruse, Niels, Gotzmann, Nadine, Gmitterová, Karin, Mollenhauer, Brit, Zerr, Inga
Format: Article
Language:English
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Summary:Several studies have addressed the utility of cerebrospinal (CSF) [alpha]-synuclein levels as a potential biomarker of [alpha]-synuclein aggregation disorders. However, its relevance in the differential diagnostic context of neurodegenerative and movement disorders is still a contentious subject. Here, we report total CSF [alpha]-synuclein levels in a cohort of clinically diagnosed [alpha]-synuclein-related disorders encompassing Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy in comparison to essential tremor and neurological control cases. [alpha]-synuclein levels in [alpha]-synuclein-related disorders were significantly lower than in controls (p < 0.001). However, in the differential diagnostic context, only Parkinson's disease cases presented significant lower [alpha]-synuclein levels compared to essential tremor and neurological controls. In cases with clinically diagnosed [alpha]-synuclein pathology, CSF [alpha]-synuclein levels showed a moderate positive correlation with CSF tau and p-tau, but not with A[beta]42 levels. Due to elevated CSF tau levels in dementia with Lewy bodies samples, tau/[alpha]-synuclein ratio showed a good clinical accuracy in discriminating controls from dementia with Lewy bodies cases (AUC = 0.8776) compared to single [alpha]-synuclein (AUC = 0.7192) and tau (AUC = 0.7739) levels. In conclusion, [alpha]-synuclein alone lacks of clinical value as a biomarker of [alpha]-synuclein-related disorders, but in combination with total tau, it may improve the diagnosis of dementia with Lewy bodies.
ISSN:0340-5354
1432-1459
DOI:10.1007/s00415-016-8259-0