The PrecivityAD™ test: Accurate and reliable LC-MS/MS assays for quantifying plasma amyloid beta 40 and 42 and apolipoprotein E proteotype for the assessment of brain amyloidosis

作者：Kristopher M. Kirmess, Matthew R. Meyer, Mary S. Holubasch, S Knapik, Yan Hu, Erin N. Jackson, Scott E. Harpstrite, Philip B. Verghese, Tim West, I. Fogelman, Joel B. Braunstein, Kevin E. Yarasheski, John H. Contois · 发表于：Clinica Chimica Acta · 年份：2021 · DOI：10.1016/j.cca.2021.05.011 · 被引用次数：136 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Alzheimer's disease research and treatments、Dementia and Cognitive Impairment Research

Background There is an unmet need for an accessible, less invasive, cost-effective method to facilitate clinical trial enrollment and aid in clinical Alzheimer’s disease (AD) diagnosis. APOE genotype affects the clearance and deposition of amyloid-beta (Aβ) with APOE 4 carriers having increased risk while APOE 2 alleles appear to be protective. Lower plasma Aβ42/40 correlates with brain amyloidosis. In response, C 2 N has developed the PrecivityAD™ test; plasma LC-MS/MS assays for Aβ isoform quantitation and qualitative APOE isoform-specific proteotyping. Methods In accord with CLIA standards, we developed and validated assay performance: precision, accuracy, linearity, limit of detection (LoD), interferences. RESULTS. Within-day precision varied from 1.5–3.0% (Aβ40) and 2.5–8.4% (Aβ42). Total (within-lab) variability was 2.7–7.7% (Aβ40) and 3.1–9.5% (Aβ42). Aβ40 quantitation was linear from 10 to 1780 pg/mL; Aβ42 was linear from 2 to 254 pg/mL. LoD was 11 and 2 pg/mL for Aβ40 and Aβ42, respectively. APOE proteotypes were 100% concordant with genotype, while LoD (fM) was much lower than APOE concentrations observed in plasma (mM). CONCLUSIONS. The PrecivityAD™ assays are precise, accurate, sensitive, and linear over a wide analytical range, free from significant interferences, and suitable for use in the clinical laboratory.