Presence of Skin α-Synuclein Deposits Discriminates Parkinson’s Disease from Progressive Supranuclear Palsy and Corticobasal Syndrome

Background: Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson’s disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited. Objective: We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD. Methods: We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin nerves by immunofluorescence. Results: Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p < 0.001, Chi-square). The two p-syn positive patients were diagnosed with PSP and CBS, respectively. Although clinical and MRI findings supported these diagnoses, both patients had some atypical features more typical of synucleinopathies. Conclusion: The detection of skin p-syn deposits may help in the differential diagnosis of parkinsonism. Indeed, in this study, all PD patients and only two out of 26 with a clinical diagnosis of PSP/CBS had skin p-syn deposits. Furthermore, these two patients showed clinical features that could suggest an atypical synucleinopathy presentation or a mixed pathology.

Case Report: Concomitant Alzheimer's and Lewy-Related Pathology Extending the Spectrum of Underlying Pathologies of Corticobasal Syndrome

Corticobasal syndrome (CBS) is clinically characterized by progressive asymmetric rigidity and apraxia together with symptoms suggestive of cortical involvement and basal ganglia dysfunction. The spectrum of neurodegenerative diseases that can manifest with CBS is wide. The associations of CBS with corticobasal degeneration, progressive supranuclear palsy, Alzheimer's disease, frontotemporal lobar degenerations, Creutzfeldt–Jakob disease, or diffuse Lewy body pathology have been reported. We describe the case of a 71-year-old woman with CBS. The histopathological examination of brain tissue revealed concomitant pathology corresponding to the limbic stage of Lewy-related pathology and the intermediate stage of Alzheimer's-type pathology. To date, there have been only a few cases with a similar combination of pathology manifesting with the CBS phenotype that have been described in the literature. The extent and distribution of pathological changes in these cases were somewhat different from ours, and significance for clinical manifestation was attributed to only one of these pathologies. In our case, we assume that both types of pathology contributed to the development of the disease, considering the presumed specific spread of both types of pathological processes according to Braak's staging. Our case expands the spectrum of neurodegenerative pathological processes that may manifest with the typical CBS phenotype. Also, it points out the importance of identifying specific biomarkers that would enable more accurate in vivo differential diagnosis and more accurate determination of the underlying pathological processes of these diseases.

Parkinsonism and Related Dementias

The differential diagnosis for dementia is wide. A slowly progressive course for parkinsonism suggests a degenerative cause and helps to narrow the differential diagnosis considerably. In patients with dementia in combination with parkinsonism (often collectively termed the parkinsonism-related dementias), the 4 most common neurodegenerative entities are 1) Lewy body dementias (which include dementia with Lewy bodies and Parkinson disease with dementia); 2) corticobasal syndrome or corticobasal degeneration; 3) Richardson syndrome or progressive supranuclear palsy; and 4) frontotemporal dementia with parkinsonism.