title: Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies.
abstract: Several studies have addressed the utility of cerebrospinal (CSF) α-synuclein levels as a potential biomarker of α-synuclein aggregation disorders. However, its relevance in the differential diagnostic context of neurodegenerative and movement disorders is still a contentious subject. Here, we report total CSF α-synuclein levels in a cohort of clinically diagnosed α-synuclein-related disorders encompassing Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy in comparison to essential tremor and neurological control cases. α-synuclein levels in α-synuclein-related disorders were significantly lower than in controls (p < 0.001). However, in the differential diagnostic context, only Parkinson's disease cases presented significant lower α-synuclein levels compared to essential tremor and neurological controls. In cases with clinically diagnosed α-synuclein pathology, CSF α-synuclein levels showed a moderate positive correlation with CSF tau and p-tau, but not with Aβ42 levels. Due to elevated CSF tau levels in dementia with Lewy bodies samples, tau/α-synuclein ratio showed a good clinical accuracy in discriminating controls from dementia with Lewy bodies cases (AUC = 0.8776) compared to single α-synuclein (AUC = 0.7192) and tau (AUC = 0.7739) levels. In conclusion, α-synuclein alone lacks of clinical value as a biomarker of α-synuclein-related disorders, but in combination with total tau, it may improve the diagnosis of dementia with Lewy bodies.
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany. franc.llorens@gmail.com.|German Center for Neurodegenerative Diseases (DZNE), Robert Koch 40, 37075, Göttingen, Germany. franc.llorens@gmail.com.
authors.forename: Franc
authors.initials: F
authors.lastname: Llorens
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Robert Koch 40, 37075, Göttingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Varges
authors.affiliation: Institute for Neuropathology, University Medical Center, Göttingen, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Kruse
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Robert Koch 40, 37075, Göttingen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gotzmann
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany.|Second Department of Neurology, Comenius University, Bratislava, Slovakia.
authors.forename: Karin
authors.initials: K
authors.lastname: Gmitterová
authors.affiliation: Institute for Neuropathology, University Medical Center, Göttingen, Germany.|Paracelsus-Elena Klinik, Center for Parkinsonism and Movement Disorders, Kassel, Germany.|Department of Neurosurgery, University Medical Center, Göttingen, Germany.
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University, Robert Koch Strasse 40, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Robert Koch 40, 37075, Göttingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid* / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D066263:Protein Aggregation, Pathological / Q000209:etiology*; D012372:ROC Curve; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Biomarker; Cerebrospinal fluid; Neurodegenerative diseases; α-Synuclein; α-Synuclein aggregation disorders