Cryo‐electron Microscopy Imaging of Alzheimer's Amyloid‐beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold

Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure these pores remains be characterized. We studied functional Aβ42-pore equivalent, created by fusing Aβ42 oligomerizing, soluble domain α-hemolysin (αHL) toxin. Our data reveal Aβ42-αHL share major structural, functional, biological properties with wild-type Aβ42-pores. Single-particle cryo-EM analysis (with an overall 3.3 Å resolution) reveals region intrinsically flexible. The will allow many features that cannot otherwise, may highly specific antigen for development immuno-base diagnostics therapies.