Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity
Stephen Zicha, Randall J. Bateman, Leslie M. Shaw, Henrik Zetterberg, Anthony W. Bannon, Wesley A. Horton, Mike Baratta, Hartmuth C. Kolb, Iwona Dobler, Yulia Mordashova, Ziad S. Saad, David Raunig, Emmanouil G. Spanakis, Yan Li, Suzanne E. Schindler, Kyle Ferber, Carrie E. Rubel, Robert Martone, Christopher J. Weber, Rebecca M. Edelmayer, Emily A. Meyers, James G. Bollinger, Erin G. Rosenbaugh, William Z. Potter, Alzheimer's Disease Neuroimaging Initiative (ADNI)
Abstract
INTRODUCTION: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. METHODS: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. RESULTS: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). DISCUSSION: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. HIGHLIGHTS: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone.