Plasma Amyloid-beta Oligomerization Tendency Predicts Amyloid PET Positivity

Abstract

Purpose: Among other emerging amyloid-targeting blood-based biomarkers, Multimer Detection System-Oligomeric Amyloid-beta (MDS-OA beta) measures dynamic changes in concentration of oligomeric amyloid-beta (OA beta), which is considered the main pathogenic culprit of Alzheimer's disease (AD), in plasma after spiking with synthetic amyloid-beta (A beta). We aimed to investigate the predictability of MDS-OA beta on amyloid positron emission tomography (PET) positivity. Patients and Methods: A total of 96 subjects who visited Seoul National University Bundang Hospital for medical check-up complaining of cognitive decline and had undergone extensive medical assessment were recruited. Amyloid statuses were dichotomized into positive or negative based on visual assessment of amyloid PET. Plasma OA beta concentration was measured by MDS-OA beta. In the previous validation study, 0.78ng/mL was established as the cut-off value and the plasma OA beta concentration higher than or equal to the cut-off value was defined as MDS-OA beta positive. Results: MDS-OA beta positivity could discriminate amyloid PET positivity with the AUC value of 0.855 (95% CI 0.776-0.933). Adding MDS-OA beta positivity to prediction models including age, MMSE score, and APOE epsilon 4 status improved performance up to the AUC value of 0.926 (95% CI 0.871-0.980). Conclusion: The A beta oligomerization tendency in plasma could predict amyloid PET positivity with high performance, and, when it is combined with age, MMSE score, and APOE epsilon 4 status, predictability was improved substantially. This suggests the potential of MDS-OA beta as a useful initial stage test in the clinical and research fields of AD.