Year: 2024
Type: article
Abstract: To the Editor: We carefully read the letter of Dr Kawada1 related to our paper reporting the prevalence of phosphorylated α-synuclein (p-α-syn) in skin nerves in very old healthy subjects, old subjects with small fiber neuropathy and 490 healthy cases from the scientific literature for a total of 531 subjects.2 In our paper, we disclosed that only 4 healthy subjects were reported to be positive for p-α-syn (1%). As underlined by Dr Kawada, a similar rate of p-α-syn positivity was recently reported (3.3%) in a study analyzing a large cohort of healthy subjects (n = 120).3 A very low positivity rate found in controls confirms that the search of the skin p-α-syn could be a highly specific tool to identify patients with an underlying synucleinopathy in vivo. Dr Kawada also reported the possibility of finding accumulations of p-α-syn in peripheral macrophages of the skin as an alternative biomarker for PD,4 although this finding has not been confirmed in other studies. However, Dr Kawada’s main criticism is related to the fact that skin biopsy is a time-consuming, expensive and invasive technique. Accordingly, he suggested to look for p-α-syn accumulations with alternative techniques that, however, are not mentioned or suggested in the letter. We agree with the Dr Kawada that a less invasive technique for detecting p-α-syn would be preferable to skin biopsy but at the moment we are not aware that the evaluation offered by a skin biopsy can be obtained with another technique. Indeed, we must emphasize that the skin biopsy presents few and negligible side effects.3,5–7 In fact, a direct comparison of skin biopsy with the other sample that can be used to evaluate misfolded α-syn, namely the CSF, underlined how skin biopsy presents lower and less important side effects than lumbar puncture.8 In addition, skin biopsy is not an expensive technique because the cost of primary and secondary antibodies to obtain p-α-syn staining is in the range of a few tens of euros in a single patient with the technique that we have described.5,7 In addition, the main instrumentation that must be used (cryostat and fluorescence microscope) is usually part of a neuropathology laboratory. Furthermore, it is not a time-consuming method considering that staining the p-α-syn is achieved in 2 days, although we agree that it is a complex technique that requires adequate and prolonged training. However, skin biopsy presents the advantage of improving the in vivo diagnostic accuracy of synucleinopathies as demonstrated in all variants of synucleinopathies, including multiple system atrophy.3,8–10 No funding was received. The authors have no conflict of interest to declare.
DOI: 10.1093/jnen/nlae089
Authors: Vincenzo Donadio, Rocco Liguori
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4401445843