Evaluation of α-synuclein as a novel cerebrospinal fluid biomarker in different forms of prion diseases

• Published in: Alzheimer's & dementia Vol. 13; no. 6; pp. 710 - 719
• Main Authors: Llorens, Franc, Kruse, Niels, Schmitz, Matthias, Gotzmann, Nadine, Golanska, Ewa, Thüne, Katrin, Zejneli, Orgeta, Kanata, Eirini, Knipper, Tobias, Cramm, Maria, Lange, Peter, Zafar, Saima, Sikorska, Beata, Liberski, Pawel P, Mitrova, Eva, Varges, Daniela, Schmidt, Christian, Sklaviadis, Theodoros, Mollenhauer, Brit, Zerr, Inga
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017
• Subjects: 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; α-Synuclein; Biomarker; Neurodegenerative diseases; Sporadic Creutzfeldt-Jakob disease; Genetic Creutzfeldt-Jakob disease; Prion diseases; Cerebrospinal fluid; ELISA
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1016/j.jalz.2016.09.013

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.