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.
Keywords: Alzheimer’s disease; Apolipoprotein E; Aβ 42/40; Beta-amyloid; Biomarkers.
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