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

Anne M. Fagan, Leslie M. Shaw, Chengjie Xiong, Hugo Vanderstichele, Mark A. Mintun, John Q. Trojanowski, Els Coart, John C. Morris, David M. Holtzman

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1137-1144
Number of pages8
JournalArchives of neurology
Volume68
Issue number9
DOIs
StatePublished - Sep 2011

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