ArticleNPJ Parkinson's disease2026
Oligomeric Alpha-Synuclein from neural-derived extracellular vesicles as possible biomarkers of non-motor symptoms in Parkinson's disease.
Article in NPJ Parkinson's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Non-motor symptoms (NMS) in Parkinson's disease (PD) are clinically impactful and lack reliable blood-based biomarkers. Neural-derived extracellular vesicles (NDEVs) enriched from serum may reflect central neurodegenerative processes. In this cross-sectional study, we examined associations between NMS burden and NDEV-associated proteins in 68 patients with PD. NDEVs were immunocaptured from serum using an anti-L1CAM approach and characterized according to MISEV guidelines. NDEV-associated oligomeric α-synuclein, SNARE complex proteins (SNAP-25, VAMP2, STX-1A), and neurotrophic factors (BDNF, GDNF, CDNF) were quantified by ELISA and related to NMS burden and PCA-derived non-motor domains, adjusting for age, sex, disease duration, MDS-UPDRS III, and levodopa equivalent daily dose (LEDD). Higher NDEV-associated oligomeric α-synuclein correlated with total NMSS score (partial Spearman's ρ = 0.252, p = 0.02) and with hallucinations (domain 4) and attention/memory (domain 5). These associations were confirmed by multivariable regression analyses. In domain-specific models, oligomeric α-synuclein was independently associated with worse cognitive and behavioral-psychotic scores, whereas higher STX-1A and lower CDNF were associated with greater affective-motivational symptom severity. No significant associations were observed for autonomic or sleep domains. These findings support NDEV-associated oligomeric α-synuclein as a candidate biomarker of non-motor symptom burden in PD and warrant longitudinal validation.
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