Preparation Protocols of A beta(1-40) Promote the Formation of Polymorphic Aggregates and Altered Interactions with Lipid Bilayers

作者：Yates Elizabeth A; Legleiter Justin^*

来源：Biochemistry, 2014, 53(45): 7038-7050.

DOI：10.1021/bi500792f

The appearance of neuritic amyloid plaques comprised of beta-amyloid peptide (A beta) in the brain is a predominant feature in Alzheimer%26apos;s disease (AD). In the aggregation process, A beta samples a variety of potentially toxic aggregate species, ranging from small oligomers to fibrils. A beta has the ability to form a _variety of morphologically distinct and stable amyloid fibrils. Commonly termed m polyorphs, such distinct aggregate species may play a role n variations of AD pathology. It has been well documented that polymorphic aggregates of A beta can be produced by changes in the chemical environment and peptide preparations. As A beta 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 A beta(1-40) preparation protocols that lead to distinct polymorphic fibril aggregates influence the interaction of A beta(1-40) with model lipid membranes. Using three distinct protocols for preparing A beta(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 A beta(1-40) promoted distinct oligorneric and fibrillar aggregates in the absence of bilayers that formed at different rate%26apos;s. Despite these differences in aggregation properties, all A beta(1-40) preparations were able to disrupt supported total brain lipid extract bilayers, altering the bilayer%26apos;s morphological and mechanical properties.

• 出版日期2014-11-18