Support for enteric nervous system pathology in prodromal PD

By Lucy Piper, Senior medwireNews Reporter

Researchers have found positive immunostaining of α-synuclein in the enteric nervous system (ENS) of patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), suggesting it may have a possible role as a biomarker for prodromal Parkinson’s disease (PD).

iRBD is one of the conditions most representative of the PD prodrome, occurring in up to 80% of patients who go on to develop the disease, Werner Poewe (Medical University of Innsbruck, Austria) and co-researchers explain.

They report that four of 17 patients with this condition stained positive with a serine 129-phosphorylated α-synuclein (pSyn) antibody in the nerve fibres or ganglia of the colonic submucosa, along with one of 19 patients with PD. By contrast, immunostaining was negative for all of the 14 healthy individuals included in the study.

“Therefore, the present findings raise the possibility that ENS pSyn immunohistochemistry could help to identify those participants with iRBD who will go on to develop clinical PD and in whom RBD could be considered a prodromal manifestation of the disease”, the researchers comment in Neurology.

They add that their findings are “broadly consistent” with the theory that the ENS may be a site of initiation for α-synuclein pathology, a major component of Lewy bodies, that subsequently spreads via the vagal nerve to the brain.

They point out, however, that the fact that only a single PD patient was positive for the marker does not fit with their suggestions and is “difficult to understand”. They speculate that once α-synuclein pathology is initiated in the ENS, rostral transmission or transport may be associated with the clearance of aggregated α-synuclein.

Studies on α-synuclein in the ENS to date have been inconsistent and Poewe and team suggest that this may be due to methodological factors.

Indeed, they found that positive immunostaining was specific to the pSyn antibody. The 15G7 α-synuclein antibody, which non-specifically binds to native α-synuclein, did not discriminate between patients and controls.

Also, depth of biopsies was critical, with pSyn immunopositivity seen in submucosal but not mucosal tissue.

In a related editorial, Marcus Unger (Saarland University, Saarbrücken, Germany) and Ryuji Sakakibara (Toho University, Sakura, Japan) say that the findings are “of notable importance”.

Despite colonic biopsies not being readily available as a diagnostic biomarker for prodromal PD, the results endorse the link between iRBD and PD and support the notion of a common pathology, they write.

“The results are compatible with current concepts of an early pathology in the ENS in PD (and iRBD) and imply that PD-related pathology might be detectable in vivo at a prodromal stage”, the editorialists conclude.

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