Very interesting to see the continuation of the work of this group following the first report in 2014...especially given the strong results presented. Phosphorylated alpha-syn in biopsies from all subjects with a syncucleinopathy (PD and PAF) and the importance of the site of sampling reiterated.
Ann Neurol. 2015 Nov 25. doi: 10.1002/ana.24567. [Epub ahead of print]
Donadio V, Incensi A, Piccinini C, Cortelli P, Giannoccaro MP, Baruzzi A, Liguori R.
OBJECTIVE:
To characterize the expression in skin nerves of native (n-syn) and misfolded phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to: 1) define the importance of n-syn and p-syn as disease biomarkers; 2) ascertain differences in abnormal synuclein skin nerve deposits.
MATERIALS AND METHODS:
We studied 30 patients including 16 well-characterized IPD and 14 patients fulfilling PAF diagnostic criteria and 15 age-matched controls. Subjects underwent skin biopsy from proximal (i.e. cervical) and distal (i.e. thigh and leg) sites to study small nerve fiber and intraneural n-syn and p-syn.
RESULTS:
PAF and IPD showed a length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. N-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any skin sample of controls but was found in all PAF and IPD patients whilst with different skin innervation. In addition, abnormal α-syn deposits were found in all analyzed skin samples in PAF but in only 49% of samples with a higher positivity rate in the proximal site in IPD.
INTERPRETATION:
1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; 2) neuritic p-syn inclusions differed in PAF and IPD suggesting a different underlying pathogenesis; 3) searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF but it is critical in IPD.
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