Project Abstract Parkinson’s Disease (PD) and atypical parkinsonian syndromes are neurodegenerative diseases in which symptoms include movement disorder, often autonomic dysfunction, and sometimes dementia. Due to high symptom overlap, patients with these diseases often are misdiagnosed leading to high levels of anxiety and depression, and to difficulty in developing therapeutic intervention. The parent grant examines candidate biomarkers for these diseases in serum and CNS-originating extracellular vesicles (EVs) isolated from the serum. However, these candidates are based on current knowledge whereas other, perhaps superior biomarkers may not yet have been discovered. Unbiased proteomics-based biomarker discovery is a promising approach but is practically challenging in CNS-originating EVs. Therefore, we will use EVs isolated from the culture media of iPSC-derived neurons from patients with the same parkinsonian diseases, and healthy controls. These studies may lead to discovery of novel biomarkers that will further aid the diagnosis, monitoring, prognosis, and treatment of parkinsonian diseases. The supplement will support a talented graduate student co-mentored by the PI and a proteomics expert. The student already has generated preliminary data demonstrating that the experiments are feasible and promising. The co-mentoring, formal classes, interaction with collaborators, and multiple professional-development opportunities will help preparing the student for a successful and productive career as a scientific researcher.