Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging

Abstract

Introduction: Levels of amyloid β peptide 42 (Aβ42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography.

Methods: CSF samples from 200 individuals underwent separate analysis for Aβ42, total tau, and phosphorylated tau-181 with automated Roche Elecsys assays. Aβ40 was measured with a commercial plate-based assay. Positron emission tomography with Pittsburgh Compound B was performed less than 1 year from CSF collection.

Results: Ratios of CSF biomarkers (total tau/Aβ42, phosphorylated tau-181/Aβ42, and Aβ42/Aβ40) best discriminated Pittsburgh Compound B-positive from Pittsburgh Compound B-negative individuals.

Discussion: CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers.

Keywords: Alzheimer's disease; Amyloid; Biomarker; Cerebrospinal fluid; Cutoff.