Preparation of a Well-Defined and Stable beta-Barrel Pore-Forming A beta 42 Oligomer

The formation of amyloid-beta peptide (A beta) oligomers at the cellular membrane is considered a crucial process that underlies neurotoxicity in Alzheimer's disease (AD). To obtain structural information on this type of oligomers, we were inspired by membrane protein approaches used to stabilize, characterize, and analyze the function of such proteins. Using these approaches, we developed conditions under which A beta 42, the A beta variant most strongly linked to the aetiology of AD, assembles into an oligomer that inserts into lipid bilayers as a well-defined pore and adopts a specific structure with characteristics of a beta-barrel arrangement. We named this oligomer beta-barrel Pore-Forming A beta 42 Oligomer (beta PFOA beta 42). Here, we describe detailed protocols for its preparation and characterization. We expect beta PFOA beta 42 to be useful in establishing the involvement of membrane-associated A beta oligomers in AD.