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

An important observation in light of the huge amount of research that is going on in this area right now...

Neurology. 2015 Jan 14. pii: 10.1212/WNL.0000000000001240. [Epub ahead of print]

Visanji NP, Marras C, Kern DS, Al Dakheel A, Gao A, Liu LW, Lang AE, Hazrati LN.

OBJECTIVE:

To determine the utility of detecting α-synuclein (αSyn) 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 αSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect αSyn in colonic mucosal biopsies from 15 patients with early PD (<3 years), 7 patients with later PD (>5 years), and 11 individuals without PD. αSyn and serine 129-phosphorylated αSyn (Ser129p-αSyn) were assessed by PET blot and conventional immunohistochemistry.

RESULTS:

PET blot-resistant aggregated αSyn and Ser129p-αSyn 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 αSyn and Ser129p-αSyn, 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 αSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of αSyn is not a useful diagnostic test for PD. The utility of detecting αSyn in the colon as a biomarker in combination with other assessments remains to be determined.