Colonic mucosal α-synuclein ruled out as Parkinson’s biomarker
medwireNews: Aggregated and hyperphosphorylated α-synuclein (αSyn) are present as frequently in the colonic mucosa of healthy people as they are in that of patients with Parkinson’s disease (PD), a study shows.
Naomi Visanji (Toronto Western Hospital, Ontario, Canada) and co-workers used the paraffin-embedded tissue (PET) blot to detect αSyn in PD patients and controls. The method was developed to improve the accuracy of detecting aggregated proteins in Creutzfeldt–Jakob disease, by degrading physiological proteins and leaving only aggregated, pathological proteins to be measured.
Visanji et al hoped using the technique would resolve issues surrounding the specificity of detecting pathological colonic mucosal αSyn in PD patients.
Indeed, as reported in Neurology, the team found that the technique was more specific than standard immunohistochemistry (IHC), detecting αSyn in 41 of 120 biopsies taken from 15 patients with early PD (diagnosed less than 3 years previously). Using IHC, αSyn was present in 107 biopsies.
Likewise, PET blot detected αSyn in 20 of 56 biopsies taken from seven patients who were diagnosed more than 5 years previously, whereas IHC detected it in 50. PET blot was also more specific for hyperphosphorylated αSyn, although the differences were not as large as for overall αSyn.
But despite its greater specificity, PET blot detected αSyn in 40 of 88 biopsies taken from 11 healthy control individuals of similar age to the PD patients, with pathological αSyn found in all 11 controls. The researchers note that, in their previous studies on postmortem brains, PET blot did not detect aggregated αSyn in the brains of people without PD, implying that αSyn aggregates in the colonic mucosa are “not necessarily pathologic”.
Indeed, both aggregated and hyperphosphorylated αSyn were markedly less frequent in the colonic mucosa of PD patients than of controls, with each appearing in just 18 of the 40 biopsies. The researchers speculate that this could shed light on the pathological process of PD, suggesting that pathological colonic αSyn aggregates might disaggregate and infiltrate the enteric and then central nervous system.
Finally, they note that their findings do not exclude that αSyn deposition in other tissues, such as the submandibular gland, could still be a useful PD biomarker. “It is possible that the PET blot may be useful in increasing the sensitivity or specificity of αSyn deposition for PD in these alternate tissues”, they conclude.
medwireNews is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015