Imaging α-synuclein protein aggregation by CEST-MRI for monitoring of synucleinopathies

Motivation: Misfolded proteins that aggregate in the brain are at the root of many neurodegenerative diseases. Goal(s): Our aim was to demonstrate that CEST can distinguish between soluble and aggregated forms, and that it is possible to monitor them in vivo. Approach: We optimized a CEST sequence in vitro on purified forms of α-synuclein and then injected them into the brain of mice to follow their propagation. Results: The CEST signal differ strongly depending on the protein conformation, and longitudinal tracking has enabled us to show that protein aggregates propagate in the brain on a scale of several months. Impact: CEST imaging can distinguish proteins in soluble or aggregated form that are at the root of many neurodegenerative diseases, making it possible to envisage CEST imaging as a non-invasive diagnostic tool for these diseases.