Innovative Skin-Based Test Enhances Diagnosis of Rare Neurodegenerative Disease

Researchers from the University Health Network (UHN) and the University of Toronto have developed a groundbreaking skin-based diagnostic test that can identify key markers of progressive supranuclear palsy (PSP). PSP is a rare and debilitating neurodegenerative disorder characterized by progressive difficulties in movement, balance, and swallowing hygiene. This new approach offers promising improvements over existing diagnostic methods, which often rely on clinical assessments and imaging, and may encounter limitations in accuracy.

The test, detailed in a recent issue of JAMA Neurology, is designed to detect unique signatures of misfolded tau proteins, which play a significant role in the pathology of PSP. Unlike traditional detection techniques that require cerebrospinal fluid analysis through lumbar puncture — a process that is invasive and not always feasible — this skin assay provides a less invasive, quicker, and potentially more accessible option.

Dr. Ivan Martinez-Valbuena, a scientific associate at the Rossy Progressive Supranuclear Palsy Centre at UHN's Krembil Brain Institute, emphasizes the importance of this advancement. “This assay is crucial for correctly identifying patients for clinical trials and will become increasingly vital as targeted, precision therapies for PSP are developed,” he states. Accurate diagnosis is essential to ensure patients receive appropriate treatments and to advance research efforts.

Neurodegenerative diseases often involve the accumulation of misfolded proteins such as alpha-synuclein or tau proteins within cells, leading to cell damage and disease progression. While detection of these proteins in cerebrospinal fluid is possible, it is often inaccessible and difficult for patients. Consequently, many patients are diagnosed based solely on symptoms, which can lead to misdiagnosis—particularly among rarer conditions like PSP. This misclassification can negatively impact clinical trials, as patients may be enrolled in studies targeting incorrect proteins.

Building upon previous research, where a test was developed to detect misfolded alpha-synuclein in skin tissue for Parkinson’s disease, the team adapted similar technology to target the specific
four-repeat tau proteins associated with PSP. Under the leadership of Gabor Kovacs, the team successfully demonstrated that disease-associated tau proteins could be detected in skin biopsies with high accuracy. When tested on samples from patients with PSP, as well as those with other neurodegenerative disorders and healthy controls, the assay showed 90% sensitivity and specificity. Notably, misfolded tau was not identified in Parkinson’s patients or healthy individuals.

This promising diagnostic tool could be integrated into a broader panel of blood and skin tests, combined with clinical data, to improve diagnostic precision. Dr. Martinez-Valbuena highlights the potential for this assay to guide personalized treatment strategies, especially as therapies targeting misfolded proteins are developed. The research team is currently validating this method in a larger cohort across multiple centers in North America and Europe to ensure its practicality outside major research hospitals.

The advancement in skin-based diagnosis marks a significant step towards earlier and more accurate detection of PSP, ultimately aiding in targeted treatment development and improving patient outcomes.