Plasma amyloid‐β oligomerization assay as a screening test for abnormal amyloid status

Abstract

AbstractBackgroundThe dynamic process of amyloid‐β (Aβ) oligomerization is considered vital for the neurotoxic effects of Aβ in Alzheimer’s disease (AD). Measuring plasma Aβ oligomerization tendency (OAβ) in blood would provide a simple and low‐cost tool for AD diagnosis. Therefore, we assessed the performance of plasma OAβ as a marker for abnormal amyloid status. We additionally evaluated the effect of long‐term storage, as this may influence plasma OAβ levels.MethodWe included 414 subjects regardless of clinical diagnosis from the Amsterdam Dementia Cohort and European Medical Information Framework for AD project (table1). Amyloid status was determined by visual read on Positron Emission Tomography (PET). Plasma OAβ was measured using the Multimer Detection System (MDS). The effect of long‐term storage on plasma MDS‐OAβ was assessed using Generalized Linear Models (GLM) including storage period, amyloid status, and their 2‐way interaction. In case of a significant 2‐way interaction, the cohort was stratified based on the median storage‐period (4 years). Age and Apolipoprotein (APOE)e4 adjusted, plasma MDS‐OAβ levels were evaluated between normal and abnormal amyloid individuals using GLM. Associations between plasma MDS‐OAβ and Aβ‐PET status were assessed using logistic regression analyses and receiver operating characteristics analyses.ResultWe found a 2‐way interaction for amyloid status and storage period on plasma MDS‐OAβ levels. In samples stored ≤4 years, but not >4 years, plasma MDS‐OAβ was higher in abnormal Aβ‐PET individuals, and could identify abnormal amyloid status with an Area Under the Curve (AUC) of 74% (95%CI:67%‐81%). Combining APOEe4 and age with plasma MDS‐OAβ revealed an AUC of 81% (95%CI: 74%‐87%; figure 1), which performed better than age and APOEe4 genotype alone (AUC: 70%, 95% CI: 63‐78, p=0.01). Using the highest Youden cutoff (45, sensitivity=76%, specificity=69%) to identify 100 individuals with abnormal Aβ‐PET status reduced the number of PET scans by 118, and lowered PET costs from 1.490.000 to 900.000 USD (40%).ConclusionPlasma MDS‐OAβ together with APOEe4 and age, has the potential to identify brain amyloidosis. Additionally, plasma MDS‐OAβ as a screener could reduce the costs may reduce the number of PET scans needed to screen for amyloidosis, which is highly relevant for clinical trials.