Alimentary, my dear Watson? The challenges of enteric α‐synuclein as a Parkinson's disease biomarker

An accurate early diagnostic test for Parkinson's disease (PD) is a critical unmet need. Recently, independent groups using different histological techniques have reported that the presence of alpha-synuclein (α-syn) in colonic biopsy tissue is able to distinguish living patients with PD from those without the disease. In addition, a further study has suggested that the presence of α-syn in colonic biopsy tissue may be evident in early or even prodromal PD. However, several questions remain regarding the translation of these findings into using the assessment of α-syn deposition in the enteric nervous system as a diagnostic biomarker for prodromal PD. Here we address critical issues related to the location and quantification of enteric α-syn, detection of α-syn with currently available histological techniques, timing of detection of α-syn deposition, and, most crucially, whether enteric α-syn can distinguish those with PD from both healthy individuals and individuals with other related diseases. We conclude that, although enteric α-syn is a very exciting prospect, further studies will be vital to determine whether enteric α-syn deposition has the potential to be the biomarker for prodromal PD that the field so desperately seeks.