Summary: A chemical assay can detect traces of Parkinson’s-related alpha-synuclein in skin samples.
Source: Iowa State University
New research demonstrates that a simple skin test can accurately identify Parkinson’s disease, proving the feasibility of this diagnostic approach. Parkinson’s disease is currently diagnosed based on clinical signs and symptoms and can only be confirmed definitively at autopsy, which means early-stage misdiagnosis is common and complicates clinical trials for new treatments.
Published in the journal Movement Disorders, the study shows that a highly sensitive chemical assay can detect abnormal clumping of the protein alpha-synuclein in small skin samples, providing a practical peripheral biomarker for Parkinson’s disease (PD). The authors suggest that this method could enable earlier and more accurate diagnosis, improving patient care and the quality of clinical trials.
“Because there is currently no simple, reliable test for early Parkinson’s disease, the potential use of skin biopsies for diagnosis could attract considerable clinical interest,” said Anumantha Kanthasamy, Distinguished Professor of Biomedical Sciences at Iowa State and lead author of the study.
The investigators performed a blinded analysis on 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND)/Brain and Body Donation Program at Banner Sun Health Research Institute. Half of the specimens were from individuals with pathologically confirmed Parkinson’s disease and half were from control subjects without neurologic disease. Using the protein aggregation assay, researchers correctly identified 24 out of 25 Parkinson’s cases while only one of the 25 control samples showed protein aggregation. Dr. Charles Adler, M.D., professor of neurology at Mayo Clinic Arizona and a co-investigator, emphasized that “these results indicate extremely high sensitivity and specificity, which are essential qualities for any diagnostic test.”
Dr. Thomas Beach, M.D., co-investigator and head of the Civin Laboratory at Banner Sun Health Research Institute, noted the practical implications: “Clinical diagnostic accuracy for early-stage PD has historically been poor, around 50–70%. Because therapeutic trials must often enroll patients at an early stage to prevent irreversible brain damage, including individuals who do not actually have PD has been a major obstacle. Improving diagnostic accuracy is the first critical step toward developing effective treatments.”
The diagnostic method evaluated in this research is the real-time quaking-induced conversion assay (RT‑QuIC), a biochemical test originally developed to detect prion diseases such as mad cow disease. Kanthasamy’s laboratory has refined and optimized RT‑QuIC to detect misfolded proteins associated with human and animal neurodegenerative disorders. In Parkinson’s disease, misfolded alpha-synuclein aggregates accumulate in the brain and cause neuronal damage. Prior research led by Adler and Beach through AZSAND has shown that these misfolded alpha-synuclein aggregates can also appear in peripheral tissues, including the skin, making skin biopsies a promising target for biomarker testing.
According to the researchers, testing skin samples with this ultra-sensitive assay could enable clinicians to diagnose Parkinson’s disease earlier in its course. Earlier detection would allow earlier intervention and make it feasible to evaluate therapies aimed at slowing or preventing progression to advanced symptoms.
About this Parkinson’s disease research news
Source: Iowa State University
Contact: Fred Love – Iowa State University
Image: The image is in the public domain
Original Research: Closed access.
“Blinded RT‑QuIC Analysis of α‑Synuclein Biomarker in Skin Tissue from Parkinson’s Disease Patients” by Anumantha Kanthasamy et al. Movement Disorders
Abstract
Blinded RT‑QuIC Analysis of α‑Synuclein Biomarker in Skin Tissue from Parkinson’s Disease Patients
Background
There is an unmet clinical need for reliable biomarkers to diagnose Parkinson’s disease, ideally from easily accessible peripheral tissues such as skin. Previous immunohistochemical studies have detected pathological alpha-synuclein (αSyn) in skin biopsies from PD patients, but sensitivity and reproducibility require improvement.
Objective
This study aims to demonstrate ultrasensitive detection of pathological αSyn in skin from PD patients using an optimized RT‑QuIC assay, supporting the potential of skin αSyn as a diagnostic biomarker for Parkinson’s disease.
Methods
Researchers applied the real‑time quaking‑induced conversion (RT‑QuIC) assay to detect pathological αSyn in human skin tissue. The assay was optimized for both frozen and formalin‑fixed, paraffin‑embedded (FFPE) skin sections. Seeding kinetics were determined for autopsied subjects, using frozen skin from 25 PD cases and 25 controls, and FFPE sections from 12 PD cases and 12 controls.
Results
In this blinded analysis, the RT‑QuIC assay identified 24 of 25 PD cases and 24 of 25 controls correctly using frozen skin tissue, corresponding to 96% sensitivity and 96% specificity. For FFPE skin sections, the assay detected 9 of 12 PD cases and 10 of 12 controls, corresponding to 75% sensitivity and 83% specificity.
Conclusions
These blinded results demonstrate the feasibility of using skin tissue and RT‑QuIC detection of pathological alpha-synuclein as a clinical diagnostic approach for Parkinson’s disease. Detecting misfolded proteins in peripheral tissues like skin may also offer a translational tool for tracking disease progression and evaluating therapeutic interventions over time.