P008 - AΒ PEPTIDES FORM ION CHANNELS IN PHOSPHOLIPID BILAYER MEMBRANES BY THE MEDIATION OF GANGLIOSIDE AT LOW CONCENTRATION
Abstract
Aims
Alzheimer’s disease (AD) is the most common neurodegenerative disorder, mainly affecting the elderly. The pathophysiology of the disease is characterized by accumulation of extracellular plaques, predominantly comprised of amyloid beta (Aβ), and cytoplasmic neurofibrillary tangles, mostly comprised of tau protein. The Aβ aggregation process is found strongly dependent on the concentration. Despite mounting evidence for the aggregation process of high Aβ concentration, little is known about the Aβoligomer formation at physiological concentrations, especially under the regulation of the cell membrane.
Methods
Here, we use liposomes to probe the interaction between diverse membrane environments and the Aβ aggregation process. We find that Aβ interacts with membrane that is rich in monosialotetrahexosylganglioside (GM1), and GM1 clusters maintain Aβ oligomers’ stability, and promote the amyloid fibril formation. We also determine the regulation of membrane constituents on Aβ aggregation and investigate the formation of Aβ ion channels at low concentrations under the regulation of GM1.
Results
Finally, we characterize the structure of Aβ ion channels by circular dichroism and mass spectrometry for computational modeling of the structure.
Conclusions
The interrogation of the formation and regulation of Aβ channel structures on membranes provide new insight into the understanding of AD pathogenesis.
