Plasma amyloid-beta oligomerization assay as a pre-screening test for amyloid status

Abstract

Objective: We assessed the performance of plasma amyloid oligomerization tendency (OA beta) as a marker for abnormal amyloid status. Additionally, we examined long-term storage effects on plasma OA beta. Methods: We included 399 subjects regardless of clinical diagnosis from the Amsterdam Dementia Cohort and European Medical Information Framework for AD project (age, 63.8 +/- 6.6; 44% female). Amyloid status was determined by visual read on positron emission tomography (PET; n(abnormal) = 206). Plasma OA beta was measured using the multimer detection system (MDS). Long-term storage effects on MDS-OA beta were assessed using general linear models. Associations between plasma MDS-OA beta and A beta-PET status were assessed using logistic regression and receiver operating characteristics analyses. Correlations between plasma MDS-OAP and CSF biomarker levels were evaluated using Pearson correlation analyses. Results: MDS-OA beta was higher in individuals with abnormal amyloid, and it identified abnormal A beta-PET with an area under the curve (AUC) of 0.74 (95% CI, 0.67-0.81), especially in samples with a storage duration < 4 years. Combining APOEe4 and age with plasma MDS-OA beta revealed an AUC of 81% for abnormal amyloid PET status (95% CI, 74-87%). Plasma MDS-OA beta correlated negatively with MMSE (r = - 0.29, p < .01) and CSF A beta 42 (r = - 0.20, p < 0.05) and positively with CSF Tau (r = 0.20, p = 0.01). Conclusions: Plasma MDS-OA beta combined with APOEe4 and age accurately identifies brain amyloidosis in a large A beta-confirmed population. Using plasma MDS-OA beta as a screener reduced the costs and number of PET scans needed to screen for amyloidosis, which is relevant for clinical trials. Additionally, plasma MDS-OA beta levels appeared affected by long-term storage duration, which could be of interest for others measuring plasma A beta biomarkers.