title: Detection of disease-associated α-synuclein in the cerebrospinal fluid: a feasibility study.
abstract: With the aim to evaluate the significance and reliability of detecting disease-specific α-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of α-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of β-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed α-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific α-synuclein was detectable in the CSF in a subset of patients with α-synuclein pathology in the brain. When combined with the analysis of total α-synuclein, the bead-assay for disease-specific α-synuclein was highly specific for PDD/DLB. Detection of disease-associated αsynuclein combined with the total levels of α-synuclein is a promising tool for the in-vivo diagnosis of α-synucleinopathies, including PDD and LBD.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria, AJ Roboscreen GmbH, Leipzig, Germany, Department of Neurology, present address: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria, and Neurobiologie, CMRR, Hospices Civils de Lyon, Université Lyon, Lyon, France.
authors.forename: Ursula
authors.initials: U
authors.lastname: Unterberger
authors.forename: Ingolf
authors.initials: I
authors.lastname: Lachmann
authors.forename: Till
authors.initials: T
authors.lastname: Voigtländer
authors.forename: Walter
authors.initials: W
authors.lastname: Pirker
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Katharina
authors.initials: K
authors.lastname: Flach
authors.forename: Uta
authors.initials: U
authors.lastname: Wagner
authors.forename: Aline
authors.initials: A
authors.lastname: Geneste
authors.forename: Armand
authors.initials: A
authors.lastname: Perret-Liaudet
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000592:standards; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods* / Q000592:standards; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D015203:Reproducibility of Results; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein