Real-time monitoring of the amyloid β 1-42 monomer-to-oligomer channel transition using a lipid bilayer system

• Published in: PNAS nexus 2024-01, Vol.3 (1), p.pgad437
• Main Authors: Numaguchi, Yuri, Tsukakoshi, Kaori, Takeuchi, Nanami, Suzuki, Yuki, Ikebukuro, Kazunori, Kawano, Ryuji
• Format: Article
• Language: English
• ISSN: 2752-6542

This study describes the observation of the transformation of monomeric amyloid β (Aβ42) into oligomers in a lipid membrane utilizing a lipid bilayer system for electrophysiological measurement. The relevance of oligomers and protofibrils in Alzheimer's disease (AD) is underscored given their significant neurotoxicity. By closely monitoring the shift of Aβ42 from its monomeric state to forming oligomeric channels in phospholipid membranes, we noted that this transformation transpired within a 2-h frame. We manipulated the lipid membrane's constitution with components such as glycerophospholipid, porcine brain total lipid extract, sphingomyelin (SM), and cholesterol (Chol.) to effectively imitate nerve cell membranes. Interesting findings showcased Chol.'s ability to foster stable oligomeric channel formation in the lipid membrane, with SM and GM1 lipids potentially enhancing channel formation as well. Additionally, the study identified the potential of a catechin derivative, epigallocatechin gallate (EGCG), in obstructing oligomerization. With EGCG present in the outer solution of the Aβ42-infused membrane, a noteworthy reduction in channel current was observed, suggesting the successful inhibition of oligomerization. This conclusion held true in both, prior and subsequent, stages of oligomerization. Our findings shed light on the toxicity of oligomers, promising invaluable information for future advancements in AD treatment strategies.