Skin biopsy may aid in early identification and differential diagnosis of Parkinson’s disease

The diagnosis of Parkinson’s disease (PD) is currently based on consensual clinical criteria. A new study reported in the Parkinson’s Disease Journal found that the presence of neuronal deposits of the biomarker phosphorylated alpha-synuclein (p-syn) in the brain and skin of patients with PD distinguishes them from individuals with symptoms of parkinsonism due to the accumulation of another protein, the tau. This development may aid in the early identification and differential diagnosis of PD among the different 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 due to the accumulation of another protein, the tau. Despite the clinical overlap with PD, PSP is characterized by 4-repeat tau deposits, primarily in the basal ganglia, brainstem, and cerebellum, and CBS is a clinical syndrome with heterogeneous underlying neuropathology , represented mainly by tauopathies but also by synucleinopathies.

Research in PD and other neurodegenerative disorders consists of finding treatments capable of stopping and ideally preventing the accumulation of the pathological proteins responsible for the various disorders. Our lab, led by Prof. Rocco Liguori and Dr. Vincenzo Donadio, has spent the past decade searching for reliable biomarkers of PD and related disorders to achieve accurate and early diagnosis.

Maria Pia Giannoccaro, PhD, Corresponding Author, Department of Biomedical and Neuromotor Sciences, University of Bologna and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

“This research grew out of the same effort. Our goal 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,” continued Dr Giannoccaro.

Investigators recruited 26 patients with PD, 26 patients with PSP (18) or CBS (8), and 26 healthy individuals from May 2014 to April 2017. All individuals underwent skin biopsy at three sites, leg , thigh and cervix. region, to study p-syn deposits in skin nerves. They found that all but two PSP/CBS patients had no cutaneous p-syn deposits, as did all healthy individuals. Conversely, all parkinsonian patients had 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 several neurodegenerative disorders occurring at the same time. Both patients had atypical features more typical of PD that might suggest an atypical presentation of synucleinopathy.

“To our knowledge, this is the largest study comparing in vivo peripheral deposition of misfolded alpha-synuclein in PD and PSP/CBS,” commented Dr. Giannoccaro. “We have shown that the presence of cutaneous p-syn deposits accurately distinguishes patients with PD from those with atypical parkinsonism. are different.

The researchers recommend further studies including larger patient samples to confirm these findings. Moreover, in the near future, it may be relevant for recruiting patients into clinical trials of potentially 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 disease, affecting around 3% of the population over the age of 65 and up to 5% of people over the age of 85.


Journal reference:

Giannoccaro, deputy, et al. (2022) Presence of α-synuclein skin deposits discriminates Parkinson’s disease from progressive supranuclear palsy and corticobasal syndrome. Journal of Parkinson’s Disease.