Study Rationale: Our understanding of Parkinson’s disease (PD) would be significantly improved if we had a way to directly monitor disease development and progression in the brain. One approach is to use extracellular vesicles (EVs) as a proxy. These membrane-enclosed sacs are shed from every cell in the body and can be collected from biofluids such as blood. We have developed methods for sequencing the RNA contained in blood-borne EVs that originated in the brain. We will compare these RNAs with RNAs from the brains of the same individuals to assess how well EVs reflect RNA changes in brain.
Hypothesis: We hypothesize that the RNA contents of EVs originating from the brain, which we will collect in accessible biofluids such as serum, will correlate with the RNA contents in postmortem brain samples.
Study Design: We will isolate EVs that originated in the brain from serum samples. We will sequence the RNA contents of those EVs and compare the RNAs that we find to the RNAs obtained from the brain of the same subject. We will be working with matched serum and brain samples from 35 subjects with very little brain pathology, 35 subjects with Alzheimer’s disease, 35 subjects with PD and 35 subjects with both PD and dementia.
Impact on Diagnosis/Treatment of Parkinson’s disease: If we can monitor the brain and its vulnerable cell populations in real time, we will be able to track disease development and progression and have an invaluable tool for understanding PD and for evaluating the effectiveness of disease-modifying therapies.
Next Steps for Development: If this proof-of-concept experiment is successful, we will examine how EV signals vary within an individual and in the larger PD population. We can then develop EVs as a tool for assessing PD risk and monitoring disease progression and therapeutic response in people with PD