Characterizations of the β-amyloid (Aβ)-membrane interaction intermediates.

Non-specific membrane disruption induced by the amyloidogenic aggregation of β-amyloid (Aβ) peptides is considered an underlying molecular mechanism of Alzheimer's disease (AD). Therefore, elucidating the membrane interruptive intermediate states of Aβ aggregates is a crucial step towards the understanding of molecular basis of AD pathology. However, such intermediate states are heterogeneous, low-abundant, and insoluble, bringing challenges for the application of high-resolution techniques. The solid-state nuclear magnetic resonance (ssNMR) spectroscopy remains the most feasible technique to characterize the structural features and molecular dynamics of the Aβ-membrane intermediate systems. Despite the capability, specific quantitative and sensitivity-enhanced ssNMR approaches, as well as membrane biophysical and/or cell-based biophysical assays, should be combined to maximize the biological relevance of the intermediate structural characterizations. In this methodology chapter, we will review the experimental and data analysis protocols that have been established in our laboratory.