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Mol Neurobiol. 2018 Mar;55(3):2249-2257. doi: 10.1007/s12035-017-0479-5. Epub 2017 Mar 21.

Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

Author information

1
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany. franc.llorens@gmail.com.
2
German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany. franc.llorens@gmail.com.
3
Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
4
Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
5
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
6
German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
7
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
8
Creutzfeldt-Jakob disease unit. Alzheimer's disease and other cognitive disorders unit. Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
9
Paracelsus-Elena Klinik, Center for Parkinsonism and Movement Disorders, Kassel, Germany.
10
Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.

Abstract

The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

KEYWORDS:

Biomarkers; Cerebrospinal fluid; ELISA; Electrochemiluminescence; Sporadic Creutzfeldt-Jakob; α-Synuclein

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