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

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Abstract

Several studies have addressed the utility of cerebrospinal (CSF) α-synuclein levels as a potential biomarker of α-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 α-synuclein levels in a cohort of clinically diagnosed α-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. α-synuclein levels in α-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 α-synuclein levels compared to essential tremor and neurological controls. In cases with clinically diagnosed α-synuclein pathology, CSF α-synuclein levels showed a moderate positive correlation with CSF tau and p-tau, but not with Aβ42 levels. Due to elevated CSF tau levels in dementia with Lewy bodies samples, tau/α-synuclein ratio showed a good clinical accuracy in discriminating controls from dementia with Lewy bodies cases (AUC = 0.8776) compared to single α-synuclein (AUC = 0.7192) and tau (AUC = 0.7739) levels. In conclusion, α-synuclein alone lacks of clinical value as a biomarker of α-synuclein-related disorders, but in combination with total tau, it may improve the diagnosis of dementia with Lewy bodies.

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Abbreviations

CSF:

Cerebrospinal fluid

PD:

Parkinson’s disease

PDD:

Parkinson’s disease dementia

DLB:

Dementia with Lewy bodies

MSA:

Multiple system atrophy

ET:

Essential tremor

AD:

Alzheimer’s disease

AUC:

Area under the curve

ROC:

Receiver operating characteristic

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgments

The work was supported by the JPND Neurodegenerative Disease Research grant: DEMTEST: Biomarker based diagnosis of rapidly progressive dementias-optimization of diagnostic protocols, 01ED1201A, by the Alzheimer-Forschungs-Initiative e.V. (AFI 12851) and by the DZNE-MiGAP study.

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    Authors and Affiliations

    1. Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany

      Franc Llorens, Matthias Schmitz, Daniela Varges, Nadine Gotzmann, Karin Gmitterová & Inga Zerr

    2. German Center for Neurodegenerative Diseases (DZNE), Robert Koch 40, 37075, Göttingen, Germany

      Franc Llorens, Matthias Schmitz, Nadine Gotzmann & Inga Zerr

    3. Institute for Neuropathology, University Medical Center, Göttingen, Germany

      Niels Kruse & Brit Mollenhauer

    4. Second Department of Neurology, Comenius University, Bratislava, Slovakia

      Karin Gmitterová

    5. Paracelsus-Elena Klinik, Center for Parkinsonism and Movement Disorders, Kassel, Germany

      Brit Mollenhauer

    6. Department of Neurosurgery, University Medical Center, Göttingen, Germany

      Brit Mollenhauer

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    1. Franc Llorens
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    Correspondence to Franc Llorens.

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    This study was conducted in compliance with the ethical standards.

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    F. Llorens, M. Schmitz and D. Varges equally contributed.

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    Llorens, F., Schmitz, M., Varges, D. et al. Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies. J Neurol 263, 2271–2277 (2016). https://doi.org/10.1007/s00415-016-8259-0

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