Mitochondrial Proteins in Putative Neuron-Derived Plasma Exosomes Are Altered in Parkinson's Disease: An Exploratory...

Mitochondrial dysfunction is central to Parkinson's disease (PD), but assessing it in vivo remains challenging. Plasma L1CAM-immunocaptured putative neuron-derived exosomes (NDEs) offer minimally invasive access to brain molecular signatures. This study investigated whether mitochondrial complex (MC) proteins in NDEs are altered in PD and explored their association with clinical features. Plasma putative NDEs were isolated from 28 patients with PD and 33 normal controls (NCs) by L1CAM immunocapture. Levels of mitochondrial subunits-NDUFS3 (Complex I), UQCRC2 (Complex III), MT-CO1 (Complex IV), and ATP5F1A (Complex V)-and the antioxidant enzyme SOD1 were quantified by ELISA. Correlations with clinical severity and diagnostic performance were analyzed. Compared with NCs, PD patients exhibited significantly lower levels of NDUFS3 and UQCRC2 in NDEs (p < 0.05, after FDR correction). NDUFS3, UQCRC2, and SOD1 showed modest inverse correlations with motor symptom severity (R = -0.26). The NDUFS3/UQCRC2 combination yielded an AUC of 0.763 (95% CI: 0.638-0.862) with 100% sensitivity and 51.5% specificity in this exploratory cohort, indicating limited discriminative capacity. These exploratory findings suggest that mitochondrial proteins within plasma putative NDEs may reflect neuronal mitochondrial alterations in PD. The NDUFS3/UQCRC2 combination represents a candidate signature warranting validation in larger cohorts.