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Abstract #4189

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

Julien Flament1, Alexis Fenyi1, Luc Bousset1, and Ronald Melki1
1Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France, Fontenay-aux-Roses, France

Synopsis

Keywords: Parkinson's Disease, CEST & MT

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.

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