title: Performance Evaluation of an Automated ELISA System for Alzheimer's Disease Detection in Clinical Routine.
abstract: The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers undermines their full-fledged introduction into routine diagnostics and clinical trials. Automation may help to increase precision and decrease operator errors, eventually improving the diagnostic performance. Here we evaluated three new CSF immunoassays, EUROIMMUNtrademark amyloid-β 1-40 (Aβ1-40), amyloid-β 1-42 (Aβ1-42), and total tau (t-tau), in combination with automated analysis of the samples. The CSF biomarkers were measured in a cohort consisting of AD patients (n = 28), mild cognitive impairment (MCI, n = 77), and neurological controls (OND, n = 35). MCI patients were evaluated yearly and cognitive functions were assessed by Mini-Mental State Examination. The patients clinically diagnosed with AD and MCI were classified according to the CSF biomarkers profile following NIA-AA criteria and the Erlangen score. Technical evaluation of the immunoassays was performed together with the calculation of their diagnostic performance. Furthermore, the results for EUROIMMUN Aβ1-42 and t-tau were compared to standard immunoassay methods (INNOTESTtrademark). EUROIMMUN assays for Aβ1-42 and t-tau correlated with INNOTEST (r = 0.83, p < 0.001 for both) and allowed a similar interpretation of the CSF profiles. The Aβ1-42/Aβ1-40 ratio measured with EUROIMMUN was the best parameter for AD detection and improved the diagnostic accuracy of Aβ1-42 (area under the curve = 0.93). In MCI patients, the Aβ1-42/Aβ1-40 ratio was associated with cognitive decline and clinical progression to AD.The diagnostic performance of the EUROIMMUN assays with automation is comparable to other currently used methods. The variability of the method and the value of the Aβ1-42/Aβ1-40 ratio in AD diagnosis need to be validated in large multi-center studies.
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Chiasserini
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Biscetti
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università di Perugia, Perugia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Farotti
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Eusebi
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvadori
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Lisetti
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università di Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baschieri
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Chipi
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Frattini
authors.affiliation: ADx NeuroSciences, Gent, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Stoops
authors.affiliation: ADx NeuroSciences, Gent, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vanderstichele
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università di Perugia, Perugia, Italy.|IRRCS Fondazione S.Lucia, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.affiliation: Laboratory of Clinical Neurochemistry, Department of Medicine, University of Perugia, Perugia, Italy.|Clinica Neurologica, Dipartimento di Medicina, Università di Perugia, Perugia, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D057205:Automation, Laboratory; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D000073216:Mental Status and Dementia Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer’s disease; amyloid; biomarker; cerebrospinal fluid; mild cognitive impairment; tau