Clinical Utility of Plasma Aβ42/40 Ratio by LC-MS/MS in Alzheimer’s Disease Assessment

Introduction Plasma A beta 42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.Methods A beta 42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for A beta 42/40 testing.Results High diagnostic sensitivity and negative predictive value (NPV) for A beta-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between A beta 42/40 values for individuals with positive vs. negative A beta-PET results. Assuming a moderate prevalence of A beta-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%.Conclusion High-throughput plasma A beta 42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.