Study Rationale: Accumulation of alpha-synuclein and tau protein aggregates are pathological hallmarks of Parkinson’s disease (PD) and Frontal Temporal Dementia (FTD), respectively. The appearance of these deposits is believed to be an early marker of disease. An ability to visualize and quantify alpha-synuclein and tau aggregates in the brain would be valuable for diagnosing PD and FTD, accurately assessing disease stage and progression, and as a tool for evaluating drugs developed to treat these disorders. In this study, we will develop imaging agents that can be used to detect alpha-synuclein and tau.
Hypothesis: Highly selective and potent alpha-synuclein and tau imaging agents for PD and FTD can be used to non-invasively assess regional deposits of these proteins and to follow their removal with therapy.
Study Design: Compounds that bind selectively to alpha-synuclein and tau deposits will be assessed using a variety of binding assays in test tubes. These lead compounds will be chemically modified and optimized to enhance their properties as potential positron emission tomography (PET) tracers for imaging alpha-synuclein and tau deposits in the brains of individuals with PD and FTD. The long-term goal of this work is to produce radioactively labeled compounds for use in PET imaging studies to non-invasively assess alpha-synuclein and tau deposits in the brains of people with PD and FTD.
Impact on Diagnosis/Treatment of Parkinson’s disease: Detection of alpha-synuclein and tau deposits in the brain of PD and FTD subjects would support early diagnosis and tracking disease progression, as well as the evaluation of drugs, currently under development, that target and remove alpha-synuclein and tau aggregates from the brain.
Next Steps for Development: Once identified and validated, our alpha-synuclein and tau PET tracers will be made available to the PD and FTD research and therapy communities for a variety of imaging applications.