BOSTON—A skin biopsy can detect alpha-synuclein in patients with Parkinson’s disease, potentially helping clinicians to make a more accurate diagnosis, researchers reported at the 2012 Annual Meeting of the American Neurological Association.
“The presence of alpha-synuclein was strongly positive in Parkinson’s disease, mild in atypical parkinsonism, and not detectable in controls,” stated Idelfonso Rodríguez-Leyva, MD, Professor of Neurology and Neurophysiology at the Universidad Autónoma de San Luis Potosí in Mexico, and colleagues. “Although these findings require further confirmation, they have the potential of improving the diagnostic accuracy of Parkinson’s disease using a minimally invasive modality.”
Skin biopsies from the lower back and cervical region were used to assess 21 patients with Parkinson’s disease and nine patients with atypical parkinsonism. In addition, 10 healthy controls underwent cervical biopsies.
Using immunohistochemistry and immunofluorescence with polyclonal antibody for alpha-synuclein, the investigators evaluated a total of 70 specimens. The presence of alpha-synuclein was expressed as a percentage and was quantified based on the number of positive cells in relation to the total.
Alpha-Synuclein in Skin Cells
Dr. Rodríguez-Leyva and his colleagues assessed the frequency of alpha-synuclein deposits in the spinous cells layer, pilosebaceous unit cells, and eccrine gland cells of patients with Parkinson’s disease and those with atypical parkinsonism. Among patients with Parkinson’s disease, 60.1% of cells in the eccrine glands, 59.0% in the pilosebaceous units, and 54.8% in the spinous layer were positive for alpha-synuclein. Alpha-synuclein was also detected in patients with atypical parkinsonism, though in substantially smaller amounts (2.7%, 2.7%, and 2.9%, respectively).
The greatest expression of alpha-synuclein was found in eccrine gland cells and pilosebaceous units, but the variability between the different structures was not significant, noted Dr. Rodríguez-Leyva. “I believe the important point is to find alpha-synuclein in those structures with absent, mild, or strong positivity,” he told Neurology Reviews.
According to Dr. Rodríguez-Leyva, Parkinson’s disease is sometimes confused with other kinds of parkinsonism—including vascular, post-infection, and posttraumatic—or even other proteinopathies such as progressive supranuclear paralysis, Alzheimer’s disease, and corticobasal degeneration.
The diagnosis of these neurodegenerative diseases is clinical, and diagnostic errors are common in the early stages, he explained. DaT scans have the power to distinguish Parkinson’s disease from normal aging, but “unfortunately, DaT imaging is not reliable for the differentiation of Parkinson’s disease from atypical parkinsonism disorders such as multiple-system atrophy and progressive supranuclear palsy, disorders in which the degree and pattern of dopamine deficit are similar to Parkinson’s disease. Structural and functional imaging studies may be helpful but have not been refined for ascertainment of diagnosis,” he said. Thus, the researchers examined alpha-synuclein pathology in the skin, with the hope of developing an accurate, minimally invasive method of diagnosing Parkinson’s disease.
Although more research is necessary to confirm the investigators’ results, the findings could potentially lead to a skin biopsy that could distinguish Parkinson’s disease from atypical parkinsonisms, said Dr. Rodríguez-Leyva. The possibility of detecting differences in the skin expression of alpha-synuclein in patients with Parkinson’s “opens a window in the study of neurodegenerative diseases,” he concluded.