Objective: This study aimed to explore cellular inflammatory and autophagic mediators in neuronal exosomes of PD and PSP.

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, rigidity, and tremor, whereas Progressive supranuclear palsy (PSP), a rare disease that disproportionately affects walking and balance, and eye movements. PD, PSP lacks reliable, non-invasive biomarkers for diagnosis and disease monitoring. Multiple cell types, including neurons, astrocytes and microglia, have been found to release exosomes and it’s ability to carry material can influence gene function and protein activity in recipient cells. Thus, accurate detection/monitoring of PD and PSP through exosome markers would be highly relevant for drug development.

Method: We immunoprecipitated Neuron-derived Extracellular Vesicles (NDEVs) by targeting neuronal marker L1CAM from serum samples of 10 PD, 10 PSP and 10 healthy controls (HC). Canonical EV markers (L1CAM, CD9,63,81) were validated using western blot and Nano-Flowcytometry. To validate the efficacy of NDEVs, crude serum samples were also compared with NDEV lysate. Sensitive Meso-scale Discovery (MSD) based biomarker assay and ELISAs were performed to explore inflammatory (TNF-α, IL-1α, TLR 2) and autophagic (mTOR, ATP6AP2) mediators. Kruskal-Wallis test with correction for multiple comparison was performed to validate these findings between groups.

Results: Particle analysis and expression of canonical EV markers showed the validation of L1CAM enrichment in our EV samples. Levels of TNF-α and IL-33 was significantly higher in PD, PSP compared to HC (p<0.05); on the other hand, autophagic mediators (mTOR, ATP6AP2) were significantly elevated in PSP compared to PD and HC (p<0.05). TLR-2, a receptor for IL-33, also showed significant expression in PSP and PD compared to HC(p<0.05). We failed to show any between group difference in these markers when crude serum samples were checked compared to NDEV lysate (p>0.05).

Conclusion: This pilot study with NDEVs explored cellular inflammatory and autophagic mediators in conditions like PD and PSP. Several markers including ATP6AP2 and mTOR may differentiate between PD and PSP with NDEV samples, whereas measurements from serum samples alone did not detect between-group differences. Large cohort studies with varied cell-based markers are needed to validate these potential peripheral biomarkers in PD, PSP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuronal-exosome-based-markers-in-parkinsons-disease-and-progressive-supranuclear-palsy/