A new tetra-plex fluorimetric assay for the quantification of cerebrospinal fluid β-amyloid42, total-tau, phospho-tau and α-synuclein in the differential diagnosis of neurodegenerative dementia

Background Differential diagnosis of neurodegenerative dementia is currently supported by biomarkers including cerebrospinal fluid (CSF) tests. Among them, CSF total-tau (t-tau), phosphorylated tau (p-tau) and β-amyloid42 (Aβ42) are considered core biomarkers of neurodegeneration. In the present work, we hypothesize that simultaneous assessment of these biomarkers together with CSF α-synuclein (α-syn) will significantly improve the differential diagnostic of Alzheimer’s disease and other dementias. To that aim, we characterized the analytical and clinical performance of a new tetra-plex immunoassay that simultaneously quantifies CSF Aβ42, t-tau, p-tau and α-syn in the differential diagnosis of neurodegenerative dementia. Methods Biomarkers’ concentrations were measured in neurological controls ( n = 38), Alzheimer’s disease ( n = 35), Creutzfeldt–Jakob disease ( n = 37), vascular dementia ( n = 28), dementia with Lewy bodies/Parkinson’s disease dementia ( n = 27) and frontotemporal dementia ( n = 34) using the new tetra-plex assay and established single-plex assays. Biomarker’s performance was evaluated and diagnostic accuracy in the discrimination of diagnostic groups was determined using partial least squares discriminant analysis. Results The tetra-plex assay presented accuracies similar to individual single-plex assays with acceptable analytical performance. Significant correlations were observed between tetra-plex and single-plex assays. Using partial least squares discriminant analysis, Alzheimer’s disease and Creutzfeldt–Jakob disease were well differentiated, reaching high accuracies in the discrimination from the rest of diagnostic groups. Conclusions The new tetra-plex assay coupled with multivariate analytical approaches becomes a valuable asset for the differential diagnosis of neurodegenerative dementia and related applications.