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.
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receiver operating characteristic
area under the curve
sporadic Creutzfeldt–Jakob disease
dementia with LBs
enzyme-linked immunosorbent assay
Parkinson’s disease dementia
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We thank Silja Köchy for indispensable technical assistance.
AV-P was funded by Georg-August University of Göttingen (Dorothea Schlözer Programme). FL was funded by the Spanish Ministry of Health–Instituto Carlos III (Miguel Servet–CP16/00041). The assay development work has been supported by the Michael J. Fox Foundation (Grant No. 10147). JQT and VM-YL were supported by NIA Grant AG-10124.
The present study was conducted according to the revised Declaration of Helsinki and Good Clinical Practice guidelines and has been approved by the local ethics committee in the University Medical Center, Göttingen (No. 9/6/08, 19/11/09, and 18/8/15). Informed consent was given by all study participants or their legal next of kin.
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The full databank of the data is available to each co-author on the paper.
Leentje Demeyer and Erik Stoops are employees of ADx NeuroSciences. Hugo Vanderstichele is a co-founder of ADx NeuroSciences and a founder of Biomarkable. All other authors declare there are no competing interests.
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Schmitz, M., Villar-Piqué, A., Llorens, F. et al. Cerebrospinal Fluid Total and Phosphorylated α-Synuclein in Patients with Creutzfeldt–Jakob Disease and Synucleinopathy. Mol Neurobiol 56, 3476–3483 (2019). https://doi.org/10.1007/s12035-018-1313-4
- Cerebrospinal fluid
- Creutzfeldt–Jakob disease
- Dementia with Lewy bodies
- Parkinson’s disease
- Phospho-serine-129 α-synuclein