Determine whether combining plasma beta amyloid 42/40 and p-tau217 could achieve >90 sensitivity and specificity in evaluating patients at an ADRC for possible Alzheimer’s disease (AD).

Advances in the ability to utilize plasma biomarkers to assess AD pathology provided new tools for assessing patients with cognitive impairment. With the emergence of anti-amyloid therapies, efficient diagnostic evaluation is needed to help identify treatment candidates accurately and timely. Combining biomarkers could provide a scalable diagnostic evaluation to identify AD patients for these therapies.

Patients from the 1Florida ADRC with clinical evaluations and PET scan data (n=276; 39.1% prevalence) were evaluated for Abeta42/40 and apoprotein E4 (ApoE4) proteotype status by LC-MS/MS and p-tau217 by immunoassay. A likelihood score model was determined for each biomarker and the combination of Abeta42/40 and p-tau217 with or without ApoE4 status. Model performance included the use of two cut points for PET positivity.

For the intended use cohort (46.0% prevalence of PET-positivity), a combination of Aβ42/40, p-tau217, and APOE4 allele count provided the best model with a receiver operating characteristic area under the curve of 0.942 and with cut points fixed at 91% sensitivity and 91% specificity yielding 88% positive predictive value (PPV), 91% negative predictive value (NPV), and 87% accuracy for identifying amyloid PET status. Inclusion of APOE4 allele count also reduced the percentage of patients with indeterminate risk by 33% (from 15% to 10%). The model and cut points categorized the real-world clinical specimens as having 42% (1,822) high, 51% (2,204) low, and 7% (300) indeterminant likelihood for PET positivity.