Nanoscale mapping of protein aggregates from biofluids

Parkinson's disease is one of several neurodegenerative conditions marked by the misfolding and subsequent clumping of proteins, which then become harmful to specific neurons. Substantial evidence suggests that the progression and spread of the disease within the brain involves the cell-to-cell transmission of pathological protein aggregates, commonly referred to as "seeds" formed from alpha-synuclein in a prion-like manner.

This conceptual model proposes that hindering the aggregation, or transmission of amyloidogenic proteins in the brain could serve as a therapeutic strategy to halt the disease's progression. The highly diverse nature of the sparsely distributed aggregates, however, has posed challenges in characterising their structure, complicating the pursuit of such a therapeutic approach.

In a joint effort with UCB Biopharma, we've previously created two single-molecule techniques capable of discerning protein aggregates from functional monomeric protein. Our application of these methods in cerebrospinal fluid demonstrated their efficacy in specifically detecting aggregates formed from alpha-synuclein. This enabled us to differentiate samples from Parkinson's disease patients from those of controls or Alzheimer's disease patients.