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Skin Biopsy Can Help Identify Patients with Parkinson’s Disease

Accumulation of the biomarker p-syn in the skin distinguishes patients with Parkinson’s disease from patients with symptoms of parkinsonism due to other neurodegenerative disorders, report scientists in a novel study published in the Journal of Parkinson’s Disease

Amsterdam, NL – The diagnosis of Parkinson’s disease (PD) is currently based on consensus clinical criteria. A novel study reported in the Journal of Parkinson’s Disease has found that the presence of neuronal deposits of the biomarker phosphorylated alpha-synuclein (p-syn) in the brain and the skin of patients with PD distinguishes them from individuals with symptoms of parkinsonism due to the accumulation of another protein, tau. This development may help the early identification and differential diagnosis of PD among the various parkinsonism subtypes.

The main parkinsonian symptoms are shared with other synucleinopathies, as well as with atypical parkinsonism, including progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), both of which are due to the accumulation of another protein, tau. Despite the clinical overlap with PD, PSP is characterized by 4-repeat tau deposits, mainly in the basal ganglia, brainstem, and cerebellum, and CBS is a clinical syndrome with a heterogeneous underlying neuropathology, represented mainly by tauopathies but also by synucleinopathies.

“Research in PD and other neurodegenerative disorders is to find treatments able to halt and ideally prevent the accumulation the pathological proteins responsible for the different disorders. Our lab, led by Prof. Rocco Liguori and Dr. Vincenzo Donadio, has spent the last decade looking for reliable biomarkers of PD and related disorders to achieve an accurate and early diagnosis,” explained corresponding author Maria Pia Giannoccaro, PhD, Department of Biomedical and Neuromotor Sciences, University of Bologna and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. 

“This research sprang from the same effort. Our aim was to see if we could distinguish PD from two potential mimics, PSP and CBS, and to explore the potential for using this approach to support clinical diagnosis,” Dr. Giannoccaro continued.

Investigators recruited 26 patients with PD, 26 patients with either PSP (18) or CBS (8), and 26 healthy individuals from May 2014 to April 2017. All individuals underwent skin biopsy in three sites, the leg, the thigh, and the cervical area, to study p-syn deposits in skin nerves. They found that all except two of the PSP/CBS patients had no skin p-syn deposits, as well as all the healthy individuals. Conversely, all PD patients showed p-syn deposition. 

The investigators were surprised by the finding that two patients diagnosed with PSP and CBS, respectively, had p-syn skin deposits. One possibility is that these two patients were misdiagnosed, however, the diagnosis was confirmed by clinical and MRI findings. Another intriguing possibility is that some patients have a mixed pathology with multiple neurodegenerative disorders occurring at the same time. Both patients had some atypical features more typical of PD that could suggest an atypical synucleinopathy presentation.

JPD 12:2 press release
Caption: Confocal microscope study of p-syn deposits in a dermal arteriole of a patient with PD (A) and a patient with CBS (B). In both cases, most of the PGP9.5-stained fibers demonstrate the presence of p-syn as neuritic inclusions (arrowheads) shown by the merged image (scalebar 50 μM) (credit: Dr. Alex Incensi).

“To our knowledge this is the largest study comparing in vivo the peripheral deposition of misfolded alpha-synuclein in PD and PSP/CBS cases,” commented Dr. Giannoccaro. “We showed that the presence of skin p-syn deposits accurately distinguishes patients with PD from those with atypical parkinsonism. Early differentiation and accurate in vivo diagnosis are important for adequate clinical management and patient care since the treatment and prognosis of PD, PSP and CBS are different. 

The investigators recommend further studies including larger samples of patients to confirm these results. Moreover, in the near future, it could be relevant for the recruitment of patients in clinical trials of potential disease-modifying therapies.

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age. 

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NOTES FOR EDITORS
Full open access study
: “Presence of Skin α-Synuclein Deposits Discriminates Parkinson’s Disease from Progressive Supranuclear Palsy and Corticobasal Syndrome” by Maria Pia Giannoccaro, Patrizia Avoni, Giovanni Rizzo, Alex Incensi, Rossella Infante, Vincenzo Donadio, and Rocco Liguori (DOI: 10.3233/JPD-212904) published in the Journal of Parkinson’s Disease, Volume 12, Issue 2 by IOS Press. The open access article is available online at: content.iospress.com/articles/journal-of-parkinsons-disease/jpd212904.

Contact
For additional information, contact Diana Murray, IOS Press (+1 718-640-5678 or d.murray@iospress.com). Journalists wishing to interview the study’s authors should contact Vincenzo Donadio (vincenzo.donadio@unibo.it).

About the Journal of Parkinson’s Disease
The Journal of Parkinson’s Disease (JPD) is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis, and treatment of Parkinson’s disease. It publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option. JPD has a 2020 Journal Impact Factor of 5.568 according to Journal Citation Reports (Clarivate, 2021) and is published by IOS Press. journalofparkinsonsdisease.com 

About IOS Press
IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in biomedical and life sciences (including neurosciences, medical informatics, cancer research, rehabilitation) and physical sciences (including computer sciences, artificial intelligence, engineering). In addition, we offer specialized services that support scientific advancement. iospress.com