Subramanian_2023_Sens.Actuators.Rep_6_

Aggregation of amyloid-beta peptide (Abeta) is hypothesized to be the primary cause of Alzheimer's disease (AD) progression. Abeta aggregation has been widely studied using conventional sensing tools like emission fluorescence, electron microscopy, mass spectroscopy, and circular dichroism. However, none of these techniques can provide cost-efficient, highly sensitive quantification of Abeta aggregation kinetics at the molecular level. Among the influences on Abeta aggregation of interest to disease progression is the acceleration of Abeta aggregation by acetylcholinesterase (AChE), which is present in the brain and inflicts the fast progression of disease due to its direct interaction with Abeta. In this work, we demonstrate the ability of a biological nanopore to map and quantify AChE accelerated aggregation of Abeta monomers to mixed oligomers and small soluble aggregates with single-molecule precision. This method will allow future work on testing direct and indirect effects of therapeutic drugs on AChE accelerated Abeta aggregation as well as disease prognosis.