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Quantifying Oligomer Populations in Real Time during Protein Aggregation Using Single-Molecule Mass Photometry.


ABSTRACT: Protein aggregation is a hallmark of many neurodegenerative diseases. The early stages of the aggregation cascade are crucial because small oligomers are thought to be key neurotoxic species, but they are difficult to study because they feature heterogeneous mixtures of transient states. We show how the populations of different oligomers can be tracked as they evolve over time during aggregation using single-molecule mass photometry to measure individually the masses of the oligomers present in solution. By applying the approach to tau protein, whose aggregates are linked to diseases including Alzheimer's and frontotemporal dementia, we found that tau existed in an equilibrium between monomers, dimers, and trimers before aggregation was triggered. Once aggregation commenced, the monomer po

SUBMITTER: Paul SS 

PROVIDER: S-EPMC9620981 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature