Endogenous A beta peptide promote A beta oligomerization tendency of spiked synthetic A beta in Alzheimer ' s disease plasma

Alzheimer's disease (AD) is the most common form of age-associated dementia. Several studies have predicted that AD is caused by the production and deposition of the beta-amyloid peptide (A beta) in the brain, which is one of pathologic hallmarks of AD. In particular, A beta oligomers are reportedly the most toxic and pathogenic of other peptide forms. We previously developed Multimer Detection System-Oligomeric Amyloid-beta (MDS-OA beta), a technique for measuring A beta oligomerization in plasma to diagnose AD. Here, we clarified the molecular sizes of oligomers that can be detected by the MDS and investigated differences in plasma spiking with a synthetic A beta peptide in the plasma of AD patients and individuals with non-AD neurological conditions. To determine A beta oligomer sizes detectable by MDS, size exclusion chromatography (SEC) was first performed on incubated samples of synthetic A beta 42 peptides. As a result, no MDS signals were observed for the A beta 42 monomer fractions, but strong signals were found for oligomers of 7-35-mers long. Also, an amplified luminescent proximity homogeneous assay-linked immunoassay (AlphaLISA) was used to confirm that synthetic A beta peptides not only recruited endogenous A beta in plasma but also induced significantly stronger seeding in AD plasma than in healthy control plasma. In addition, the absence of the MDS signals in A beta-depleted plasma confirmed that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous A beta in plasma. Therefore, the MDS-OA beta measurement of oligomerization differences in plasma after incubation with spiked synthetic A beta peptides has significant potential in AD diagnosis.