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.
Neuronally-Derived Extracellular Vesicles Transforming Growth Factor Beta-1 Levels in Progressive Supranuclear Palsy
Tolomeo A. M.;
2025
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.
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