Objective: This cross-sectional observational study aims to quantify total skin Tau levels in Parkinson’s disease (PD) patients and explore their association with clinical symptoms.

Background: Tau protein has been implicated in the pathophysiology of PD, with some studies suggesting it may even precede α-synuclein aggregation. While α-synuclein pathology in the peripheral nervous system (PNS) is well established, the role of Tau at this level remains unclear. Skin biopsy provides a tissue-specific window into PNS pathology and allows the quantification of peripheral Tau. Although a few studies have compared skin Tau levels between PD and other neurodegenerative disorders, to our knowledge no study has specifically examined potential differences in skin Tau protein levels within the PD population.

Method: We obtained distal leg 3-mm skin biopsies from PD patients and quantified total Tau using ELISA as previously described (1). Clinical variables included disease duration and motor (MDS-UPDRS), cognitive (PD-CRS), and non-motor scales (MDS-NMS).

Results: We included 18 PD patients with a median age of 68 years and 61% male (Table). After adjustment for age and sex, skin Tau levels in PD patients correlated positively with disease duration (ρ = 0.524, permutation p = 0.026). Patients in higher disease duration tertiles showed progressively greater Tau levels (p = 0.016) (Figure). No significant associations were found with motor, cognitive, or non-motor scores.

Conclusion: These exploratory findings provide the first evidence that peripheral Tau increases with disease duration in PD independent of age. Longitudinal studies are needed to establish whether skin Tau could serve as a biomarker of disease progression. Future research should also clarify whether elevated skin Tau reflects neurodegenerative changes in the central nervous system, peripheral nerves, or both.

Table

Figure

References: 1. I. Ruiz-Barrio, A. Vázquez-Oliver, A. Puig-Davi, E. Rivas-Asensio, J. Perez-Perez, C. Fernandez-Vizuete, A. Horta-Barba, G. Olmedo-Saura, N. Salvat-Rovira, F. Sampedro, E. Vacchi, G. Melli, J. Pagonabarraga, J. Kulisevsky, S. Martinez-Horta, Skin Tau Quantification as a Novel Biomarker in Huntington’s Disease, Movement Disorders 39 (2024) 2067–2074. https://doi.org/10.1002/mds.29989.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/skin-tau-quantification-as-a-potential-degeneration-biomarker-in-parkinsons-disease/