Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42

Abstract

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-β oligomers (AβOs) 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 AβOs. Methods To characterize Aβ in the blood, plasma was spiked with synthetic amyloid-β (Aβ) and incubated over time. Then, the MDS was used to monitor the dynamic changes of AβO levels in the plasma. Results Increasing concentrations of AβOs 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 Aβ spiked into the blood plasma of patients with AD, but that of not elderly normal control subjects, induced dynamic changes in the formation of AβOs over time. AβOs were detected by the MDS, which is a useful blood-based assay with high sensitivity and specificity for AD diagnosis.

Keywords

• Multimer detection system
• Alzheimer’s disease
• Amyloid-β
• Oligomers
• Blood biomarker
• Synthetic amyloid-β