2025 American Academy of Neurology Abstract Website

Objective:

This analysis retrospectively evaluated the ability of plasma biomarkers to identify Alzheimer’s disease (AD) clinical trial participants with positive amyloid beta (Aβ)-positron emission tomography (PET) results and explored plasma biomarker utility for prescreening in AD clinical trials.

Background:

PRX012 is a novel humanized IgG1κ investigational monoclonal antibody designed for subcutaneous administration that targets the N-terminus of Aβ and binds with high affinity and avidity to aggregated forms of Aβ, including protofibrils and plaques. PRX012 is being evaluated in the ASCENT Phase 1 clinical program in participants with early AD.

Design/Methods:

Plasma concentrations of Aβ42, Aβ40, ptau181, and ptau217 were analyzed with high-performance liquid chromatography-mass spectrometry (HPLC-MS) in up to 555 participants screened for clinical trial inclusion who had Aβ-PET results. Receiver operating characteristic (ROC) analyses evaluated biomarker ability to detect Aβ at ≥ 30 centiloids per Aβ-PET.

Results:

Plasma biomarkers correlated linearly with Aβ-PET. Performance status (area under the ROC curve) for detecting Aβ positivity was 0.77 for Aβ_42/40(n=555), 0.82 for ptau181 (n=196), and 0.95 for ptau217 (n=183).

Conclusions:

ROC values for the evaluated biomarkers were consistent with those previously reported. ptau217 had the highest accuracy at predicting Aβ-PET positivity. These results suggest that ptau217 prescreening could decrease the need for Aβ-PET testing, supporting the use of AD plasma biomarkers as minimally invasive tools for clinical trial prescreening.