Summary: A chemical assay can detect traces of Parkinson’s related alpha-synuclein from skin samples.
Source: Iowa State University
New research shows a simple skin test can accurately identify Parkinson’s disease, demonstrating for the first time the feasibility of the method. Currently diagnosed by clinical signs and symptoms but only definitively diagnosed at autopsy, Parkinson’s disease is commonly misdiagnosed early in the disease course, complicating clinical trials of potential treatments.
The study, published in the scientific journal Movement Disorders, shows how a chemical assay can detect clumping of the protein alpha-synuclein in skin samples to help diagnose Parkinson’s disease (PD). The study’s authors said using the assay can lead to earlier detection of PD and better clinical trials.
“Since there’s no easy and reliable test available for the early diagnosis of Parkinson’s disease at present, we think there will be a lot interest in the potential use of skin samples for diagnosis,” said Anumantha Kanthasamy, Distinguished Professor of Biomedical Sciences at Iowa State and lead author of the study.
The researchers conducted a blinded study of 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND)/Brain and Body Donation Program based at Banner Sun Health Research Institute. Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. Using the protein assay correctly diagnosed 24/25 Parkinson’s disease patients and only 1/25 controls had the protein clumping. Dr. Charles Adler, M.D., professor of neurology at Mayo Clinic Arizona, a co-investigator of the study, notes that “these results indicate tremendously high sensitivity and specificity which is critical for a diagnostic test.”
“The clinical diagnostic accuracy for early-stage PD has been quite poor, only around 50-70%. And since clinical trials really need to be done at an early stage to avoid further brain damage, they have been critically hampered because they have been including large percentages of people who may not actually have the disease,” said Dr. Thomas Beach, MD, a co-investigator of the study and head of the Civin Laboratory at Banner Sun Health Research Institute. “Improving clinical diagnostic accuracy is, in my view, the very first thing we need to do in order to find new useful treatments for PD.”
The research centers on a method known as the real-time quaking induced conversion assay, a test that was originally developed to detect mad cow disease. Kanthasamy’s laboratory has spent several years optimizing the assay for detecting misfolded proteins in similar human and animal disorders. Parkinson’s disease arises from misfolded alpha-synuclein proteins that accumulate in the brain leading to neuronal damage. Adler and Beach have led research in AZSAND that has found these misfolded alpha-synuclein proteins also collect in other body tissues as well, including the skin.
Kanthasamy said testing skin samples could lead to earlier detection of Parkinson’s disease. Earlier diagnosis could allow physicians to test therapeutic strategies designed to slow or prevent the development of advanced symptoms, he said.
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
Blinded RT‐QuIC Analysis of α‐Synuclein Biomarker in Skin Tissue from Parkinson’s Disease Patients
An unmet clinical need in Parkinson’s disease (PD) is to identify biomarkers for diagnosis, preferably in peripherally accessible tissues such as skin. Immunohistochemical studies have detected pathological α‐synuclein (αSyn) in skin biopsies from PD patients albeit sensitivity needs to be improved.
Our study provides the ultrasensitive detection of pathological αSyn present in the skin of PD patients, and thus, pathological αSyn in skin could be a potential biomarker for PD.
The real‐time quaking‐induced conversion assay was used to detect pathological αSyn present in human skin tissues. Further, we optimized this ultra‐sensitive and specific assay for both frozen and formalin‐fixed paraffin‐embedded sections of skin tissues. We determined the seeding kinetics of the αSyn present in the skin from autopsied subjects consisting of frozen skin tissues from 25 PD and 25 controls and formalin‐fixed paraffin‐embedded skin sections from 12 PD and 12 controls.
In a blinded study of skin tissues from autopsied subjects, we correctly identified 24/25 PD and 24/25 controls using frozen skin tissues (96% sensitivity and 96% specificity) compared to 9/12 PD and 10/12 controls using formalin‐fixed paraffin‐embedded skin sections (75% sensitivity and 83% specificity).
Our blinded study results clearly demonstrate the feasibility of using skin tissues for clinical diagnosis of PD by detecting pathological αSyn. Moreover, this peripheral biomarker discovery study may have broader translational value in detecting misfolded proteins in skin samples as a longitudinal progression marker.