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Neurology. 2015 Feb 10;84(6):609-16.

Colonic mucosal a-synuclein lacks specificity as a biomarker for Parkinson disease.

Abstract

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 aSynin the colon as a biomarker in combination with other assessments remains to be determined.

PMID:
25589666
PMCID:
PMC4335990
DOI:
10.1212/WNL.0000000000001240
[Indexed for MEDLINE]
Free PMC Article

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