Preparation protocols of aβ(1-40) promote the formation of polymorphic aggregates and altered interactions with lipid bilayers.

The appearance of neuritic amyloid plaques comprised of β-amyloid peptide (Aβ) in the brain is a predominant feature in Alzheimer's disease (AD). In the aggregation process, Aβ samples a variety of potentially toxic aggregate species, ranging from small oligomers to fibrils. Aβ has the ability to form a variety of morphologically distinct and stable amyloid fibrils. Commonly termed polymorphs, such distinct aggregate species may play a role in variations of AD pathology. It has been well documented that polymorphic aggregates of Aβ can be produced by changes in the chemical environment and peptide preparations. As Aβ and several of its aggregated forms are known to interact directly with lipid membranes and this interaction may play a role in a variety of potential toxic mechanisms associated with AD, we determine how different Aβ(1-40) preparation protocols that lead to distinct polymorphic fibril aggregates influence the interaction of Aβ(1-40) with model lipid membranes. Using three distinct protocols for preparing Aβ(1-40), the aggregate species formed in the absence and presence of a lipid bilayers were investigated using a variety of scanning probe microscopy techniques. The three preparations of Aβ(1-40) promoted distinct oligomeric and fibrillar aggregates in the absence of bilayers that formed at different rates. Despite these differences in aggregation properties, all Aβ(1-40) preparations were able to disrupt supported total brain lipid extract bilayers, altering the bilayer's morphological and mechanical properties.