Ion Channel Activity of Amyloid-beta Peptides in Artificial Bilayer Membranes: a Comparison of Different Preparation Techniques

Abstract

Alzheimer's disease (AD), an ultimately fatal neurodegenerative disorder, is characterized by the presence of plaques containing fibrillar aggregates of amyloid-beta (Aβ) peptides. These peptides, with 39-43 amino acids, especially Aβ(1-40) and Aβ(1-42), are the major components of plaques formed in the brain of patients with AD. Both peptides aggregate rapidly in aqueous solution to form Aβ oligomers as well as Aβ fibrils. An increasing number of evidence suggests that Aβ especially in non fibrillar forms interacts to cell membrane by forming an ion channel or pores through the membrane. One approach to study the mechanism of Aβ is to examine the ion channel activity of Aβ on lipid membrane. A challenge of studying ion channel of Aβ is the difficulty in obtaining the ion channel activity consistently. This study summarizes the 4 different methods of preparation of Aβ(1-40) and Aβ(1-42) which can form ion channel activity on the artificial membrane. We also provide the information on characterization of structural properties, size and kinetics of aggregation of Aβ corresponding to each method of preparation. Our studies may be useful for those who are interested in ion channel approach of Aβ as well as other peptides which share common characteristics in forming ion channel and involve with other amyloid diseases.