Abstract #3939

Longitudinal In Vivo Mapping of Alpha-Synuclein Aggregation in Parkinson’s Disease Using rNOE Imaging

Jannik Prasuhn^1,2,3,4,5, Jae-Jin Song^1,6,7, Fatih Akkentli^1,6, Tae-In Kam^1,6, Yuguo Li^2,8, Qing Zeng^2,8, Zijiang Yang², Sajad Mohammed Ali⁹, Linda Knutsson^1,2,9, Valina L Dawson^1,6,7,10, Ted M Dawson^1,6,7,11, Peter CM van Zijl^2,8, and Nirbhay N Yadav^2,8

¹Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Neurology, University-Medical Center Schleswig-Holstein, Lübeck, Germany, ⁴Institute of Neurogenetics, University of Lübeck, Lübeck, Germany, ⁵Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany, ⁶Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁷Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁸Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁹Department of Medical Radiation Physics, Lund University, Lund, Sweden, ¹⁰Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ¹¹Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Synopsis

Keywords: Parkinson's Disease, CEST / APT / NOE

Motivation: To develop a marker of protein aggregation in Parkinson’s disease (PD), where alpha-synuclein deposition and aggregation contribute to neurodegeneration and disease progression.

Goal(s): To investigate whether longitudinal rNOE changes follow the dynamics of protein aggregation in a PD mouse model with gut-initiated alpha-synuclein pathology.

Approach: Longitudinal rNOE imaging was conducted at 6, 9, and 12 months. Mapping of rNOE signals was performed over time as the pathology advanced from the gut to the brain.

Results: Elevated rNOE signals were observed in brain regions impacted by PD pathology, particularly hindbrain and midbrain, interpreted as an increase in protein aggregation that correlates with disease advancement.

Impact: rNOE imaging has potential as a surrogate biomarker for protein aggregation changes associated with Parkinson’s disease (PD) progression. This methodology has the potential to guide the development of therapies targeting protein aggregation, advancing neuroprotective strategies and disease management in PD.

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