In our study, we used atomic force microscopy (AFM) to image the amyloid-beta (Aβ1-42) oligomers, which are the pathological proteins in Alzheimer’s Disease (AD). The oligomers are spherical particles with diverse sizes ranging from a few nanometers to hundreds of nanometers, indicated as bright spots in the cover image of the June 18 issue of Biophysical Journal. They readily bind to cellular membranes and can damage the membrane in multiple ways, inducing cytotoxicity.

We used commercially available Aβ1-42 peptides and incubated them in sodium solutions to obtain small soluble amyloid oligomers, which are considered the most toxic species. The oligomers were deposited on mica and imaged by AFM in the air to confirm their aggregation state. Next, we used AFM to visualize amyloid-membrane interactions in an aqueous environment to visualize the amyloid damaging effects in model membranes. We are seeking and investigating membrane-targeted agents including trehalose, melatonin, and lithium to protect lipid membranes from Aβ’s toxicity as a strategy for AD prevention. Further information about our work can be found at https://uwaterloo.ca/leonenko-research-group/.

 — Yue Xu, Teresa Filice, and Zoya Leonenko