title: Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD.
abstract: The identification of reliable diagnostic tools for the differential diagnosis between sporadic Creutzfeldt-Jakob Disease (sCJD) and Alzheimer's disease (AD) remains impeded by the existing clinical, neuropathological and molecular overlap between both diseases. The development of new tools for the quantitative measurement of biomarkers is gaining experimental momentum due to recent advances in high-throughput screening analysis and with the optimization of assays for their quantification in biological fluids, including cerebrospinal fluid (CSF). Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve clinical quality performance in a variety of sample types due to its high sensitivity and dynamic range. Here, we quantified the CSF levels of Tau-protein, β-amyloid 1-42 (Aβ42) and α-synuclein, as important biomarkers in CSF used in the differential diagnosis of neurodegenerative disorders in 12 AD, 12 sCJD and 12 control cases by singleplex ECL-based technology. Its performance has been compared to classical enzyme-linked immunosorbent assays (ELISA) to confront their clinical accuracy. ECL-based technology validates previous data obtained with ELISA and presents a higher performance in the discrimination of three analysed groups as determined by increased area under the curve (AUC) values for the three biomarkers. Importantly, α-synuclein levels detected by ECL allow an excellent discrimination between sCJD cases and AD and control cases, unveiling a new clinical approach for the differential diagnosis of sCJD.
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany. franc.llorens@gmail.com.
authors.forename: Franc
authors.initials: F
authors.lastname: Llorens
authors.affiliation: Institute for Neuropathology, University Medical Center Göttingen, 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 and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shafiq
authors.affiliation: Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil.
authors.forename: José Eriton Gomes
authors.initials: JE
authors.lastname: da Cunha
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gotzman
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Saima
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Thune
authors.affiliation: Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil.
authors.forename: João Ricardo Mendes
authors.initials: JR
authors.lastname: de Oliveira
authors.affiliation: 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.
authors.forename: Brit
authors.initials: B
authors.lastname: Mollenhauer
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center, Georg-August University and German Center for Neurodegenerative Diseases (DZNE), Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid*; D003937:Diagnosis, Differential; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008163:Luminescent Measurements / Q000379:methods*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; Biomarkers; Cerebrospinal fluid; Creutzfeldt–Jakob disease; ELISA; Electrochemiluminescence-based detection system; Neurodegeneration