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 APOE4 carriers having increased risk while APOE2 alleles appear to be protective. Lower plasma Aβ42/40 correlates with brain amyloidosis. In response, C2N 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.
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 APOE4 carriers having increased risk while APOE2 alleles appear to be protective. Lower plasma Aβ42/40 correlates with brain amyloidosis. In response, C2N 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.
Authors: Yan Hu; Kristopher M Kirmess; Matthew R Meyer; Gil D Rabinovici; Constantine Gatsonis; Barry A Siegel; Rachel A Whitmer; Charles Apgar; Lucy Hanna; Michio Kanekiyo; June Kaplow; Akihiko Koyama; David Verbel; Mary S Holubasch; Stephanie S Knapik; Jason Connor; John H Contois; Erin N Jackson; Scott E Harpstrite; Randall J Bateman; David M Holtzman; Philip B Verghese; Ilana Fogelman; Joel B Braunstein; Kevin E Yarasheski; Tim West Journal: JAMA Netw Open Date: 2022-04-01
Authors: Suzanne E Schindler; Thomas K Karikari; Nicholas J Ashton; Rachel L Henson; Kevin E Yarasheski; Tim West; Mathew R Meyer; Kristopher M Kirmess; Yan Li; Benjamin Saef; Krista L Moulder; David Bradford; Anne M Fagan; Brian A Gordon; Tammie L S Benzinger; Joyce Balls-Berry; Randall J Bateman; Chengjie Xiong; Henrik Zetterberg; Kaj Blennow; John C Morris Journal: Neurology Date: 2022-04-21 Impact factor: 11.800