Objective: To determine the utility of detecting a-synuclein (aSyn) in colonic mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease (PD). Methods:We used the paraffin-embedded tissue (PET) blot, which degrades physiologic nonaggregated aSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect aSyn in colonic mucosal biopsies from 15 patients with early PD (,3 years), 7 patients with later PD (.5 years), and 11 individuals without PD. aSyn and serine 129-phosphorylated aSyn (Ser129p-aSyn) were assessed by PET blot and conventional immunohistochemistry.Results: PET blot-resistant aggregated aSyn and Ser129p-aSyn was present in 12 of 15 individuals with early PD, 7 of 7 individuals with later PD, and 11 of 11 control subjects. The number of biopsies positive by PET blot relative to conventional immunohistochemistry was significantly lower in both PD groups compared with the control group for both aSyn and Ser129p-aSyn, whereas routine immunohistochemistry was positive more often in PD, but was positive in as many as 9 of 11 control individuals.Conclusion: Strong evidence of the presence of aggregated hyperphosphorylated aSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of aSyn is not a useful diagnostic test for PD. The utility of detecting aSyn in the colon as a biomarker in combination with other assessments remains to be determined. An accurate diagnostic test for early or prodromal Parkinson disease (PD) is a significant unmet need. Studies suggesting that abnormal deposition of a-synuclein (aSyn) may originate in the peripheral autonomic nervous system, 1,2 coupled with evidence of a prion-like spread of synucleinopathy, 3 have generated much interest in evaluating enteric nervous system (ENS) aSyn to assess early PD neuropathology before disease spread and long before markers reliant on advanced disease are affected. 4 Several recent studies of aSyn staining in colonic tissue from living patients with PD report sensitivities ranging from 72% to a remarkable 100%. [5][6][7] However, the description of some degree of aSyn labeling in controls in these studies and reports of aSyn in colonic tissue from individuals without PD have raised concerns regarding specificity. 8,9 The aim of the present study was to optimize the immunohistochemical detection of aSyn in colonic biopsies by adapting the paraffin-embedded tissue (PET) blot, a method developed to increase sensitivity and specificity of detecting aggregated proteins in a related proteinopathy, Creutzfeldt-Jakob disease. The PET blot degrades nonaggregated proteins allowing the selective detection of remaining, presumably pathologic, protein aggregates.

Dilated Virchow‐Robin (VR) spaces are usually not considered to be symptomatic. We present three cases presenting with atypical clinical features, which otherwise had clinical/imaging findings consistent with idiopathic Parkinson's disease. In all cases, an isolated large VR space in the basal ganglia contralateral to the side of symptom onset was observed. We propose that the atypical features could be associated with the mass effect of a significantly enlarged VR space, which would cause a dysfunction downstream from the presynaptic nigrostriatal dopaminergic system.