Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.
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.
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany. franc.llorens@gmail.com.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany. franc.llorens@gmail.com.
Franc
F
Llorens
Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
Niels
N
Kruse
Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
André
A
Karch
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Matthias
M
Schmitz
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Saima
S
Zafar
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Nadine
N
Gotzmann
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Ting
T
Sun
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Silja
S
Köchy
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Tobias
T
Knipper
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Maria
M
Cramm
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Ewa
E
Golanska
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Beata
B
Sikorska
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Pawel P
PP
Liberski
Creutzfeldt-Jakob disease unit. Alzheimer's disease and other cognitive disorders unit. Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Raquel
R
Sánchez-Valle
German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Andre
A
Fischer
Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany.|Paracelsus-Elena Klinik, Center for Parkinsonism and Movement Disorders, Kassel, Germany.|Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
Brit
B
Mollenhauer
Clinical Dementia Center, Department of Neurology, University Medical Center Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Göttingen, Robert Koch Stasse 40, 37075, Göttingen, Germany.
Inga
I
Zerr
D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D051844:alpha-Synuclein
Biomarkers; Cerebrospinal fluid; ELISA; Electrochemiluminescence; Sporadic Creutzfeldt-Jakob; α-Synuclein