Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, Total tau, and P-tau₁₈₁ for identifying alzheimer disease amyloid plaque pathology

Background: Cerebrospinal fluid (CSF) biomarkers of Alzheimer disease (AD) are currently being considered for inclusion in revised diagnostic criteria for research and/or clinical purposes to increase the certainty of antemortem diagnosis. Objective: To test whether CSF biomarker assays differ in their ability to identify true markers of underlying AD pathology (eg, amyloid plaques and/or neurofibrillary tangles) in living individuals. Design: We compared the performances of the 2 most commonly used platforms, INNOTEST enzyme-linked immunosorbent assay and INNO-BIA AlzBio3, for measurement of CSF β-amyloid (Aβ) and tau proteins to identify the presence of amyloid plaques in a research cohort (n=103). Values obtained for CSF Aβ1-42, total tau, and phosphorylated tau 181 (p-tau181) using the 2 assay platforms were compared with brain amyloid load as assessed by positron emission tomography using the amyloid imaging agent Pittsburgh compound B. Setting: The Knight Alzheimer's Disease Research Center at Washington University in St Louis, Missouri.Subjects: Research volunteers who were cognitively normal or had mild to moderate AD dementia. Results: The 2 assay platforms yielded different (approximately2- to 6-fold) absolute values for the various analytes, but relative values were highly correlated. The CSF Aβ1-42 correlated inversely and tau and p-tau181 correlated positively with the amount of cortical Pittsburgh compound B binding, albeit to differing degrees. Both assays yielded similar patterns of CSF biomarker correlations with amyloid load. The ratios of total tau to Aβ1-42 and p-tau₁₈₁ to Aβ1-42 outperformed any single analyte, including Aβ1-42, in discriminating individuals with vs without cortical amyloid. Conclusions: The INNOTEST and INNO-BIA CSF platforms perform equally well in identifying individuals with underlying amyloid plaque pathology. Differences in absolute values, however, point to the need for assay-specific diagnostic cutoff values.