Neuronally‐Derived Extracellular Vesicles Transforming Growth Factor Beta‐1 Levels in Progressive Supranuclear Palsy

Abstract Background Differentiating progressive supranuclear palsy (PSP) from other parkinsonian disorders may be challenging. Objectives To investigate the role of transforming growth factor beta‐1 (TGFβ1) in PSP. Methods A total of 33 PSP, 39 Parkinson's disease (PD), 8 multiple system atrophy (MSA) patients, and 50 healthy controls (HC) were enrolled. TGFβ1 levels, including both active and inactive forms (latency‐associated peptide [LAP]‐TGFβ1), were measured in serum, total extracellular vesicles (EVs), and neuronally‐derived EVs (NDEVs) using microfluidic assays and ELISA. Results PSP patients exhibited a marked increase in TGFβ1 and LAP‐TGFβ1 levels in NDEVs, while no differences were observed across groups in serum or total EVs. Receiver operating characteristic (ROC) analysis demonstrated outstanding performance in differentiating PSP from non‐PSP patients (TGFβ1, area under the curve [AUC]: 0.97; LAP‐TGFβ1, AUC: 1.00), HC, AUC: 1.00). Conclusions This study highlights TGFβ1 and LAP‐TGFβ1 in NDEVs as promising blood‐based non‐invasive biomarkers for PSP diagnosis, paving the way for further research on these proteins in PSP. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.