Study Rationale: Many neurodegenerative disorders are caused by a toxic buildup of insoluble protein aggregates. In Parkinson’s disease (PD), accumulation of alpha-synuclein contributes to the death of dopamine-producing cells and disease pathology. Currently, the diagnosis of these diseases only takes place after the appearance of symptoms or signs of motor dysfunction. The development of highly specific and sensitive imaging agents for these abnormal aggregations would enable early detection and the accurate monitoring of disease progression, which would improve our understanding of the underlying disease mechanisms and potentially lead to the discovery of more effective therapeutics.
Hypothesis: We hypothesize that we can identify and develop radiolabeled tracers that can be used to detect aggregates of alpha-synuclein or tau protein by the functional imaging technique positron imaging tomography (PET).
Study Design: The goal of this study is to identify a radiotracer for imaging insoluble protein aggregates in synucleinopathies and the tauopathies by PET imaging. We will synthesize radioactively labeled variations of our engineered PET probes and test their ability to bind selectively to alpha-synuclein and tau. Successive iterations will be used to refine and identify those tracers with the greatest affinity and specificity for alpha-synuclein and tau.
Impact on Diagnosis/Treatment of Parkinson’s disease: PET radiotracers that can image either alpha-synuclein or tau will be of value in the clinical diagnosis of CNS disorders and for monitoring the effectiveness of treatment strategies aimed at reducing the amounts of these proteins in the brains of people with PD.
Next steps for development: PET tracers for alpha-synuclein and tau can be optimized to enhance image quality, facilitating the development of improved diagnostics and therapeutics.