Skin Samples May Aid Early Diagnosis of Parkinson’s, Study Suggests

A new method, originally developed to diagnose mad cow disease, shows effectiveness in measuring the buildup of alpha-synuclein in the skin of Parkinson’s disease patients, a new study reports.

According to study authors, the findings indicate that using easily collectable patient skin samples may be a feasible method to diagnose the disease early.

Findings were reported in the study “Blinded RT‐QuIC Analysis of α‐Synuclein Biomarker in Skin Tissue from Parkinson’s Disease Patients” published in the journal Movement Disorders.

Parkinson’s diagnosis is based mostly on clinical symptoms, with a confirmation possible only by post-mortem brain tissue analysis. Moreover, the overlap of symptoms with other diseases also contributes to lower clinicians’ ability to diagnose the disease at its early stages, when therapeutic interventions are more likely to succeed.

“The clinical diagnostic accuracy for early-stage PD [Parkinson’s disease] 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,” Thomas Beach, MD, said in a press release. Beach is head of the Civin Laboratory at Banner Sun Health Research Institute, Arizona, and a co-investigator of the study.

“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,” Beach said.

Certain biomarkers have been used to complement current diagnostic tools, such as the buildup of misfolded alpha-synuclein protein aggregates, or clumps — a hallmark of Parkinson’s — within the central nervous system (brain and spinal cord). These protein aggregates are toxic and trigger the death of dopaminergic neurons — those responsible for releasing the brain chemical dopamine, which is needed to control brain cell activity and function and whose levels are diminished in Parkinson’s patients.

This buildup of misfolded alpha-synuclein is typically seen in post-mortem brain tissue samples, but it also can be detected using other sources, such as the cerebrospinal fluid (CSF) — the fluid surrounding the brain and spinal cord that is usually collected via a spinal tap.

However, the collection of CSF is invasive and has been linked with an increased risk of infection and headaches. That is why more readily and easily available biological sources that allow for a faster diagnosis are needed.

Increasing evidence suggests that deposits of alpha-synuclein also can be found in nerve cells of the skin in patients with Parkinson’s. However, the methods used to detect these protein aggregates were laborious and lacked sensitivity — a test’s ability to correctly identify those with the disease.

In this study, researchers at the Iowa State University and colleagues assessed the efficacy of a method called “real-time quaking-induced conversion” (RT-QuIC) protein misfolding assay to detect alpha-synuclein in the skin. This method was developed originally to detect mad cow disease (formally known as bovine spongiform encephalopathy), which is thought to be caused by the deposition of misfolded prion proteins.

They analyzed 25 frozen autopsy skin tissue samples taken from the scalp of patients with Parkinson’s and 25 taken from elderly people without dementia or Parkinson’s who served as controls. Samples were provided by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND)/Brain and Body Donation Program of the Banner Sun Health Research Institute.

After a first test to optimize the method, researchers then tested RT-QuIC in the 50 frozen skin tissue samples they had obtained from patients and controls. They tested the RT-QuIC method in a blinded manner, meaning researchers were unaware of which samples came from patients and which came from controls.

After analysis and unblinding, results showed the optimized RT-QuIC method correctly identified the presence of protein clumps in 24 of the 25 patient skin samples, while it found no signs of these aggregates in 24 of the 25 control skin samples, rendering it a sensitivity and a specificity of 96% each. (A test’s specificity refers to its ability to correctly identify those without the disease.)

“These results indicate tremendously high sensitivity and specificity which is critical for a diagnostic test,” said Charles Adler, MD, professor of neurology at Mayo Clinic Arizona, and a co-investigator of the study.

They also tested the RT-QuIC in chemically fixed skin samples from 12 patients and 12 controls. Again, the results showed that RT-QuIC correctly identified the protein aggregates in nine of the 12 patient samples, and their absence in 10 of the 12 control samples. These results showed that despite having a worse performance in fixed samples, RT-QuIC still had a sensitivity of 75% and a specificity of 83%, making it an effective method for assessing the presence of misfolded alpha-synuclein in stored skin samples.

Overall, “our blinded study results clearly demonstrate the feasibility of using skin tissues for clinical diagnosis of PD,” by detecting misfolded alpha-synuclein aggregates, the researchers wrote.

“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, PhD, professor of Biomedical Sciences at Iowa State and the study’s lead investigator.