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

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 (A beta) with APOE4 carriers having increased risk while APOE2 alleles appear to be protective. Lower plasma A beta 42/40 correlates with brain amyloidosis. In response, C2N has developed the PrecivityAD (TM) test; plasma LC-MS/MS assays for A beta 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% (A beta 40) and 2.5-8.4% (A beta 42). Total (within-lab) variability was 2.7-7.7% (A beta 40) and 3.1-9.5% (A beta 42). A beta 40 quantitation was linear from 10 to 1780 pg/mL; A beta 42 was linear from 2 to 254 pg/mL. LoD was 11 and 2 pg/mL for A beta 40 and A beta 42, respectively. APOE proteotypes were 100% concordant with genotype, while LoD (fM) was much lower than APOE concentrations observed in plasma (mM). CONCLUSIONS. The PrecivityAD (TM) assays are precise, accurate, sensitive, and linear over a wide analytical range, free from significant interferences, and suitable for use in the clinical laboratory.

Automated summary

The PrecivityAD (TM) test developed by C2N quantifies A beta isoforms and APOE isoform-specific proteotyping accurately and with high precision. The results show that the test is sensitive, linear over a wide analytical range, free from significant interferences, and suitable for use in clinical laboratories.