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Scientists succeeded in detecting Parkinson's disease through a minimally invasive skin biopsy - years before the patient becomes noticeably ill.
Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's. Pathologically, it is characterized by the presence of α-synuclein-rich Lewy bodies. The clinical diagnosis of Parkinson's disease has remained a challenge for most physicians and is often only recognized at a later stage. This diagnosis usually occurs at a time when about 80% of the dopaminergic nerve endings and up to 50% of the nerve cells in the substantia nigra are already irreversibly destroyed. This fact underlines the need for disease-specific biomarkers at an early stage of the disease.
Würzburg and Marburg (Germany) neurologists have published a pioneering research paper on the early diagnosis of Parkinson's disease in the journal Acta Neuropathologica. Their research marks a possible milestone in diagnostics, especially with regards to pre-symptomatic Parkinson's disease therapy.
The detection of the biomarker α synuclein has been considered the gold standard in the diagnosis of Parkinson's disease for years, however, at a post-mortem stage in the brain. As early as 2014, Würzburg-based scientists were able to show that α-synuclein not only deposits in the brain but also in the skin. About 50% of the Parkinson's patients examined at that time had detectable pathological protein deposits in the small nerve fibers of the skin.
In their latest study, neurologists have gone one step further. The aim was to find out whether α-synuclein could already be used as a biomarker in the prodromal phase of Parkinson's disease. For this purpose, the scientists recruited patients suffering from REM sleep behavior disorders. The sleep disorder is accompanied by vivid, often frightening dreams and conspicuous movements in dream sleep. It is considered a characteristic early symptom of Parkinson's disease. About 85% of those affected develop Parkinson's disease within 15 to 20 years.
The group of patients examined in Würzburg and Marburg from December 2014 to July 2016 consisted of 18 patients with REM sleep disorders, 25 patients with early Parkinson's disease and 20 healthy control subjects. The four skin biopsies (5mm) taken from each subject on the back and legs were examined for deposits of phosphorylated α-synuclein in the dermal nerve fibers using double immunofluorescence staining. In addition, a nuclear medical examination (FP-CIT-SPECT) was used to determine the density of presynaptic dopamine transporters, perform olfactory function tests and calculate the probability quotient for prodromal Parkinson's symptoms.
In 10 out of 18 patients with REM sleep disorders, phosphorylated α synuclein with a sensitivity of 56% was detected. In 20 out of 25 patients with early Parkinson's disease, sensitivity to pathological protein deposits was 80%. In the healthy control subjects, however, no deposits were found. The percentage of skin structures innervated by phosphorylated α-synuclein-positive fibers correlated negatively with dopamine transporter binding and olfactory function.
The scientists see great potential in this diagnostic method due to the ease with which it is carried out and the high specificity of the examination. This could make it possible to identify patients affected at an early stage of Parkinson's disease and include them in clinical studies to test disease-modifying drugs.
1. Doppler K et al. Dermal phospho-alpha-synuclein deposits confirm REM sleep behavior disorder as prodromal Parkinson's disease. Acta Neuropathologica 2017; DOI: 10.1007/s00401-017-1684-z
2. Joint press release of the German Society of Neurology (DGN) and the German Parkinson Society (DPG); Milestone: Skin test allows early diagnosis of Parkinson's disease (02/2017)