Neuron-Derived Extracellular Vesicles for Biomarker Discovery in Neurodegeneration

Presently, it is impossible to measure biomarkers in the blood that can detect Parkinson’s Disease early and monitor its progression. Our goal is to isolate tiny nanoscale-sized packets from the blood containing the contents of brain cells. These packets are called extracellular vesicles (EVs). Our goal is to capture EVs released specifically from brain neurons, so we can “read out” their RNA and protein profiles and apply them to study the course of neurodegenerative diseases in patients. To accomplish this goal, we will develop methods to isolate brain-specific EVs using unbiased computational and experimental techniques. We will develop robust isolation techniques to capture EVs based on specific surface protein markers. After isolation, we will use a new ultrasensitive protein measurement technology and high-throughput RNA sequencing to characterize the contents of these EVs. These methods can transform our current understanding of the course and progression of neurodegeneration.

The team developed ultrasensitive Single Molecule Array (Simoa) assays for the EV markers CD9, CD63, CD81 to analyze and quantitate EVs in biological fluids. They used these assays to evaluate and improve methods of isolating EVs from CSF and plasma (1). Having established optimized methods of EV isolation, they evaluated the previously used, putative neuronal EV marker, L1CAM, and found that it was not associated with EVs (2). The team is exploring other markers for neuronal EV isolation.