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

ABSTRACT

OBJECTIVE: We assessed the performance of plasma amyloid oligomerization tendency (OAß) as a marker for abnormal amyloid status. Additionally, we examined long-term storage effects on plasma OAß. 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; nabnormal = 206). Plasma OAß was measured using the multimer detection system (MDS). Long-term storage effects on MDS-OAß were assessed using general linear models. Associations between plasma MDS-OAß and Aß-PET status were assessed using logistic regression and receiver operating characteristics analyses. Correlations between plasma MDS-OAß and CSF biomarker levels were evaluated using Pearson correlation analyses. RESULTS: MDS-OAß was higher in individuals with abnormal amyloid, and it identified abnormal Aß-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-OAß revealed an AUC of 81% for abnormal amyloid PET status (95% CI, 74-87%). Plasma MDS-OAß correlated negatively with MMSE (r = - 0.29, p < .01) and CSF Aß42 (r = - 0.20, p < 0.05) and positively with CSF Tau (r = 0.20, p = 0.01). CONCLUSIONS: Plasma MDS-OAß combined with APOEe4 and age accurately identifies brain amyloidosis in a large Aß-confirmed population. Using plasma MDS-OAß 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-OAß levels appeared affected by long-term storage duration, which could be of interest for others measuring plasma Aß biomarkers.