Abstract

The questions raised by Dr. Khan are interesting, but need clarification. First, skin nerve α-synuclein deposits are a reliable biomarker of synucleinopathies,1–3 helping to differentiate these disorders from diseases of different origins. Accordingly, through skin biopsy, pure autonomic failure was differentiated from acquired autonomic neuropathies,4 idiopathic Parkinson disease from tauopathies or vascular parkinsonisms,2 and dementia with Lewy bodies from Alzheimer disease, frontotemporal dementia, or vascular dementia.1 As postmortem studies demonstrated,5 current clinical diagnostic criteria for synucleinopathies have a considerable error rate, leading to possible misdiagnosis with disorders of different origins. A reliable biomarker is important to improve clinical management, decreasing the misdiagnosis of synucleinopathies. Furthermore, the possibility to differentiate different phenotypes of synucleinopathy by skin biopsy is an important aim, on which we are working. However, early data suggested that the distribution of α-synuclein deposits throughout proximal and distal skin sites may be helpful to identify peculiar patterns,3 although more data are needed to achieve an extensive picture of synucleinopathies.

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