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Mol Neurobiol. 2018 Aug 22. doi: 10.1007/s12035-018-1313-4. [Epub ahead of print]

Cerebrospinal Fluid Total and Phosphorylated α-Synuclein in Patients with Creutzfeldt-Jakob Disease and Synucleinopathy.

Author information

1
Department of Neurology, University Medical Center Goettingen, Goettingen, Germany. matthias.schmitz@med.uni-goettingen.de.
2
Department of Neurology, University Medical Center Goettingen, Goettingen, Germany. annavillarpique@gmail.com.
3
Department of Neurology, University Medical Center Goettingen, Goettingen, Germany. franc.llorens@gmail.com.
4
Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Barcelona, Spain. franc.llorens@gmail.com.
5
Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. franc.llorens@gmail.com.
6
Second Department of Neurology, Comenius University, Bratislava, Slovakia.
7
Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.
8
ADx NeuroSciences, Technologiepark 4, Ghent, Belgium.
9
Center for Neurodegenerative Research and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

Abstract

High levels of total α-synuclein (t-α-synuclein) in the cerebrospinal fluid (CSF) were reported in sporadic Creutzfeldt-Jakob disease (sCJD). The potential use of t-α-synuclein in the discrimination of Lewy body dementias (i.e., Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB)) is still under investigation. In addition, phospho-serine-129 α-synuclein (p-α-synuclein) has been described to be slightly increased in the CSF of synucleinopathies. Here, we analyzed t-α-synuclein and p-α-synuclein concentrations and their ratio in the context of differential diagnosis of neurodegenerative diseases. We quantified the levels of CSF t-α-synuclein and p-α-synuclein in a cohort of samples composed of neurological controls (NC), sCJD, PDD, and DLB by means of newly developed specific enzyme-linked immunosorbent assays. T-α-synuclein and p-α-synuclein were specifically elevated in sCJD compared to other disease groups. The area under the curve (AUC) values for t-α-synuclein were higher for the discrimination of sCJD from dementias associated to Lewy bodies as compared to the use of p-α-synuclein. A combination of both markers even increased the diagnostic accuracy. An inverse correlation was observed in CSF between t-α-synuclein and p-α-synuclein, especially in the DLB group, indicating a disease-relevant association between both markers. In conclusion, our data confirm t-α-synuclein and p-α-synuclein as robust biomarkers for sCJD and indicate the potential use of colorimetric t-α-synuclein ELISAs for differential diagnosis of dementia types.

KEYWORDS:

Cerebrospinal fluid; Creutzfeldt–Jakob disease; Dementia with Lewy bodies; Parkinson’s disease; Phospho-serine-129 α-synuclein; T-α-synuclein

PMID:
30136097
DOI:
10.1007/s12035-018-1313-4

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