Dynamic changes of oligomeric amyloid beta levels in plasma induced by spiked synthetic A beta(42)

Abstract

Background: A reliable blood-based assay is required to properly diagnose and monitor Alzheimer's disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-beta oligomers (A beta Os) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect A beta Os. Methods: To characterize A beta in the blood, plasma was spiked with synthetic amyloid-beta (A beta) and incubated over time. Then, the MDS was used to monitor the dynamic changes of A beta O levels in the plasma. Results: Increasing concentrations of A beta Os were observed in the plasma of patients with AD but not in the plasma of normal control subjects. The plasma from patients with AD (n = 27) was differentiated from that of the age-matched normal control subjects (n = 144) with a sensitivity of 83.3% and a specificity of 90.0%. Conclusions: Synthetic A beta spiked into the blood plasma of patients with AD, but that of not elderly normal control subjects, induced dynamic changes in the formation of A beta Os over time. A beta Os were detected by the MDS, which is a useful blood-based assay with high sensitivity and specificity for AD diagnosis.