Project Summary Parkinson’s Disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and a major cause of disability in individuals over 65 years of age. PD belongs to a spectrum of diseases termed the “synucleinopathies”, defined by the progressive aggregation of insoluble fibrillary a-synuclein, and includes other disorders such as multiple system atrophy and Lewy body dementia. Currently, there are no objective tests that can be used to definitively diagnose PD. In addition, differential diagnosis of synucleinopathies is very challenging and relies heavily on a physician's clinical evaluation. A critical goal in the field is to reliably identify synucleinopathies at early, asymptomatic stages of the disease, to allow the best chance for correct disease modifying or preventative treatments to be effective. This proposal aims to develop a small molecule fluorescent retinal contrast agent as a novel diagnostic for PD and other related synucleinopathies.