A Kinetic Map of the Influence of Biomimetic Lipid Model Membranes on Aβ42 Aggregation

• DOI: 10.1021/acschemneuro.2c00765
• Publication Date: 2022-12-27T18:55:20Z
• Authors: Kevin N. Baumann; Greta Šneiderienė; Michele Sanguanini; Matthias Schneider; Oded Rimon; Alicia González Díaz; Heather Greer; Dev Thacker; Sara Linse; Tuomas P. J. Knowles; Michele Vendruscolo
• Keywords: 0303 health sciences; Amyloid beta-Peptides; Lipid Bilayers; cryo-electron microscopy; Peptide Fragments; protein aggregation; Kinetics; 03 medical and health sciences; Biomimetics; Alzheimer Disease; amyloid β; Humans; aggregation kinetics; lipid membranes; Alzheimer’s disease; Research Article

The aggregation of the amyloid β (Aβ) peptide is one molecular hallmarks Alzheimer's disease (AD). Although Aβ deposits have mostly been observed extracellularly, various studies also reported presence intracellular assemblies. Because these aggregates might play a role in onset and progression AD, it important to investigate their possible origins at different locations cell along secretory pathway precursor protein, from which derived by proteolytic cleavage. Senile plaques found AD are largely composed 42-residue form (Aβ42). Intracellularly, Aβ42 produced endoplasmatic reticulum (ER) Golgi apparatus. Since lipid bilayers shown promote Aβ, this study, we measure effects membrane composition on vitro kinetics Aβ42. By using large unilamellar vesicles model cellular membranes locations, including inner outer leaflets plasma membrane, late endosomes, ER, apparatus, show that inhibited ER membranes. These results provide preliminary map suggest an evolutionary optimization prevent Aβ.