Skin Samples May Improve Earlier Diagnosis of Parkinson Disease

A skin test to detect clumping of alpha-synuclein (α‐synuclein), an abnormal protein suggested to have a central role in the pathogenesis of Parkinson disease (PD), may assist in improving earlier detection of the condition, according to study findings published in Movement Disorders.

With no definitive approach to diagnosing PD without postmortem autopsy, current standards of diagnosis rely on clinical signs and symptoms. These factors have contributed to common misdiagnoses early in the disease course, which study author Thomas Beach, MD, head of the Civin Laboratory at Banner Sun Health Research Institute, notes in a statement has complicated clinical trials investigating the efficacy of novel PD therapies.

“The clinical diagnostic accuracy for early-stage PD has been quite poor, only around 50% to 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 Beach. “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.”

In prior research, Beach and fellow study author Charles Adler, MD, professor of neurology at Mayo Clinic Arizona, investigated a method known as the real-time quaking induced conversion assay. After several years of optimizing the assay to detect misfolded proteins in similar human and animal disorders, both researchers found that misfolded α‐synuclein proteins accumulate in body tissues in addition to the brain, including the skin.

Building on these findings, researchers conducted a blinded study of 50 skin samples from autopsied subjects, 25 each from patients with and without PD, provided by the Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program based at Banner Sun Health Research Institute.

Utilizing the protein assay to examine these frozen skin tissues, researchers correctly diagnosed 24 of the 25 patients with PD (96% sensitivity and 96% specificity), with only 1 of the 25 controls showing to have the protein clumping. Conversely, 9 of 12 patients with PD and 10 of 12 controls were detected to have accumulation of α‐synuclein via formalin‐fixed paraffin‐embedded skin sections, which resulted in a sensitivity of 75% and specificity of 83%.

“These results indicate tremendously high sensitivity and specificity which is critical for a diagnostic test,” said Adler in a statement.

In examining the study findings, lead study author Anumantha Kanthasamy, PhD, distinguished professor of biomedical sciences at Iowa State University, said in the study’s accompanying press release that testing skin samples could lead to earlier detection of PD, which can then allow physicians to test therapeutic strategies designed to slow or prevent the development of advanced symptoms.

“Our blinded study results clearly demonstrate the feasibility of using skin tissues for clinical diagnosis of PD by detecting pathological α‐synuclein,” concluded the study authors. “Moreover, this peripheral biomarker discovery study may have broader translational value in detecting misfolded proteins in skin samples as a longitudinal progression marker.”

Reference

Kanthasamy A, Beach TG, Adler CH, et al. Blinded RT‐QuIC analysis of α‐synuclein biomarker in skin tissue from Parkinson disease patients. Mov Disord. Published online September 22, 2020. doi:10.1002/mds.28242