Category: Parkinsonism, Atypical: PSP, CBD
Objective: To ascertain the presence of misfolded tau species in the skin of Progressive Supranuclear Palsy (PSP) patients and evaluate its utility as a potential biomarker for the disease.
Background: The absence of a reliable, non-invasive diagnostic assay to diferenciate PSP from Parkinson’s disease (PD) and multiple system atrophy (MSA) is still an unmet clinical need. Recent research from our group has highlighted peripheral nervous system involvement in tauopathies, revealing misfolded tau species in cranial and spinal nerves of PSP patients. Building upon this insight, we hypothesized that similar tau pathology might be present in the skin of PSP patients.
Method: We developed a novel 4R-Tau seeding amplification assay (SAA) capable of detecting minute quantities of misfolded 4R-Tau. Performance of this assay was assessed in post-mortem brain and cervical skin biopsies from 25 subjects (PSP=7, PD=11, MSA=7), as well as in vivo cervical skin biopsies from 52 PSP, 21 PD, 22 MSA patients, and 19 healthy controls. Tau levels were measured via western blotting and ELISA.
Results: In post-mortem skin samples, tau protein presence was confirmed in all subjects using ELISA and western blot. 4R-Tau seeding was evident in 6/7 PSP patients, contrasting with none in MSA and PD cohorts (n=18). Intriguingly, tau isoform distribution varied between skin and brain. In the in vivo cohort, 4R-Tau seeding was detected in 45/52 PSP patients and only 4/62 PD, MSA, and healthy controls, yielding 87% sensitivity and 94% specificity for PSP diagnosis.
Conclusion: This study delineates the presence of 4R-Tau seeding in PSP patient skin, offering a novel biomarker with potential diagnostic implications. Moreover, our streamlined detection protocol presents a minimally invasive mean of distinguishing PSP from PD and MSA. These findings mark a significant advance in understanding the pathological basis of PSP and hold promise for refining diagnostic approaches and patient stratification in clinical trials for parkinsonian disorders.
References: 1. Tanaka H, Martinez-Valbuena I, Forrest SL, Couto B, Reyes NG, Morales-Rivero A, Lee S, Li J, Karakani AM, Tang-Wai DF, Tator C, Khadadadi M, Sadia N, Tartaglia MC, Lang AE, Kovacs GG. Distinct involvement of the cranial and spinal nerves in progressive supranuclear palsy. Brain. 2023 Nov 16:awad381. doi: 10.1093/brain/awad381. Epub ahead of print. PMID: 37972275.
2. Martinez-Valbuena I, Lee S, Santamaria E, Irigoyen JF, Forrest S, Li J, Tanaka H, Couto B, Reyes NG, Qamar H, Karakani AM, Kim A, Senkevich K, Rogaeva E, Fox SH, Tartaglia C, Visanji NP, Andrews T, Lang AE, Kovacs GG. 4R-Tau seeding activity unravels molecular subtypes in patients with Progressive Supranuclear Palsy. bioRxiv [Preprint]. 2023 Sep 29:2023.09.28.559953. doi: 10.1101/2023.09.28.559953. PMID: 37808843; PMCID: PMC10557711.
To cite this abstract in AMA style:
I. Martinez-Valbuena, D. Olszewska, M. Sousa, T. Abkur, N. Bendahan, N. Reyes, M. Emamikhah Abarghouei, C. Ghadery, L. Armengou Garcia, J. Liao, C. Tan, SM. Fereshtehnejad, H. Alotibi, JC. Vargas-Gonzalez, NC. Dimal, J. Li, P. Bhakta, R. Cheung, J. Sasitharan, N. Visanji, S. Fox, C. Tartaglia, A. Lang, G. Kovacs. Dermal 4R-Tau seeding as a novel biomarker for Progressive Supranuclear Palsy [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/dermal-4r-tau-seeding-as-a-novel-biomarker-for-progressive-supranuclear-palsy/. Accessed June 15, 2025.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/dermal-4r-tau-seeding-as-a-novel-biomarker-for-progressive-supranuclear-palsy/