Evaluation of α-synuclein as a novel cerebrospinal fluid biomarker in different forms of prion diseases
Abstract Introduction Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. Methods We established...
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| Published in: | Alzheimer's & dementia Vol. 13; no. 6; pp. 710 - 719 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Language: | English |
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01-06-2017
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| Abstract | Abstract Introduction Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. Methods We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic ( n = 234) and genetic ( n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease ( n = 278), and in the neurologic control group ( n = 111). Results An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic CJD cases showed increased CSF α-synuclein values. No increased α-synuclein levels were detected in non-CJD cases with rapid progression course. Discussion Detection of α-synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non-prion disease cases. These data highlight the utility of CSF α-synuclein quantification in front of classical CSF biomarkers in clinical routine. |
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| AbstractList | Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context.
We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111).
An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic CJD cases showed increased CSF α-synuclein values. No increased α-synuclein levels were detected in non-CJD cases with rapid progression course.
Detection of α-synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non-prion disease cases. These data highlight the utility of CSF α-synuclein quantification in front of classical CSF biomarkers in clinical routine. INTRODUCTIONAccurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context.METHODSWe established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111).RESULTSAn optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic CJD cases showed increased CSF α-synuclein values. No increased α-synuclein levels were detected in non-CJD cases with rapid progression course.DISCUSSIONDetection of α-synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non-prion disease cases. These data highlight the utility of CSF α-synuclein quantification in front of classical CSF biomarkers in clinical routine. Abstract Introduction Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. Methods We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic ( n = 234) and genetic ( n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease ( n = 278), and in the neurologic control group ( n = 111). Results An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic CJD cases showed increased CSF α-synuclein values. No increased α-synuclein levels were detected in non-CJD cases with rapid progression course. Discussion Detection of α-synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non-prion disease cases. These data highlight the utility of CSF α-synuclein quantification in front of classical CSF biomarkers in clinical routine. Introduction Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. Methods We established the clinical parameters for prion disease diagnosis for the quantification of CSF α‐synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111). Results An optimal cutoff value of 680 pg/mL α‐synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt‐Jakob disease (CJD). Genetic CJD cases showed increased CSF α‐synuclein values. No increased α‐synuclein levels were detected in non‐CJD cases with rapid progression course. Discussion Detection of α‐synuclein in the CSF of patients with suspected CJD is a valuable diagnostic test reaching almost full discrimination from non‐prion disease cases. These data highlight the utility of CSF α‐synuclein quantification in front of classical CSF biomarkers in clinical routine. |
| Author | Sikorska, Beata Gotzmann, Nadine Schmitz, Matthias Zerr, Inga Kanata, Eirini Llorens, Franc Liberski, Pawel P. Kruse, Niels Schmidt, Christian Knipper, Tobias Zafar, Saima Cramm, Maria Lange, Peter Thüne, Katrin Zejneli, Orgeta Sklaviadis, Theodoros Mollenhauer, Brit Golanska, Ewa Mitrova, Eva Varges, Daniela |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27870938$$D View this record in MEDLINE/PubMed |
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| Keywords | α-Synuclein Biomarker Neurodegenerative diseases Sporadic Creutzfeldt-Jakob disease Genetic Creutzfeldt-Jakob disease Prion diseases Cerebrospinal fluid ELISA |
| Language | English |
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| Snippet | Abstract Introduction Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial... Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in... Introduction Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in... INTRODUCTIONAccurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in... |
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| SubjectTerms | Aged alpha-Synuclein - cerebrospinal fluid Biomarker Biomarkers - cerebrospinal fluid Cerebrospinal fluid Cohort Studies Diagnosis, Differential ELISA Enzyme-Linked Immunosorbent Assay Genetic Creutzfeldt-Jakob disease Humans Middle Aged Neurodegenerative diseases Neurology Prion diseases Prion Diseases - cerebrospinal fluid Sensitivity and Specificity Sporadic Creutzfeldt-Jakob disease α-Synuclein |
| Title | Evaluation of α-synuclein as a novel cerebrospinal fluid biomarker in different forms of prion diseases |
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