Detection of amyloid beta oligomers toward early diagnosis of Alzheimer's disease


Hwang SS, Chan H, Sorci M, Van Deventer J, Wittrup D, Belfort G and Walt D.

Anal Biochem. 2018 Sep 26. pii: S0003-2697(18)30440-8


Amyloid β (Aβ) peptide accumulation in the brain is considered to be one of the hallmarks of Alzheimer's disease. Here, we compare two analytical techniques for detecting neurotoxic Aβ1-42 oligomers - Quartz Crystal Microbalance with Dissipation (QCM-D) and Single Molecule Array (Simoa). Both detection methods exploit a feature of the monoclonal antibody bapineuzumab, which targets N-terminal residues 1-5 of Aβ with high affinity and use it as both a capture and detection reagent. Assays developed with the two methods allow us to specifically recognize neurotoxic Aβ1-42 oligomers and higher aggregates such as fibrils but discriminate against Aβ1-42 monomer species. We find that for detection of Aβ1-42 oligomers, Simoa was roughly 500 times more sensitive than the QCM-D technique with limits of detection of 0.22 nM and 125 nM, respectively.