Abstract
The observation showing that Lewy type synucleinopathy (LTS), the pathological hallmark of Parkinson’s disease (PD), is found in the gut of almost all PD subjects led to a substantial amount of research to develop a diagnostic procedure in living patients based on endoscopically obtained gastrointestinal biopsies. However, the existing studies have provided conflicting results regarding the sensitivity and specificity of gastrointestinal biopsies for the detection of LTS. We therefore undertook a multi-center staining and blinded judging of a common set of slides from colonic biopsies to determine the optimal protocol for the detection of LTS. Four different immunohistochemical methods, developed in four separate expert laboratories, were evaluated for their sensitivity and specificity to detect enteric LTS. Test sets of formalin-fixed, paraffin-embedded sections from biopsies of 9 PD subjects and 3 controls were stained with the 4 methods and graded by 4 different observers. Four types of staining morphology (granular staining in the lamina propria, perivascular/vascular wall staining in the submucosa, lacy-granular pattern in the submucosa and epithelial cell nuclear staining) were variably observed in the slides stained by the 4 methods. Positive alpha-synuclein staining was observed by all 5 judges in most of the slides from control cases, regardless of the staining methods that were used. Moreover, none of the tested method or staining pattern had a specificity and sensitivity more than 80 % regarding to PD. Overall, our study suggest that the tested methods are not adequate for the prediction of PD using gastrointestinal biopsies. Future studies are warranted to test new immunostaining methods.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0305-8) contains supplementary material, which is available to authorized users.
Highlights
Since the discovery of aggregated and phosphorylated alpha-synuclein as the primary component of Lewy pathology, immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis of Parkinson’s disease (PD) [1, 2]
Selection of subjects and formalin-fixed paraffin-embedded blocks Nine PD patients were included in this study, chosen from among 29 subjects that had been recruited from the movement disorder clinic in Nantes University Hospital, France for a previously published study of enteric synucleinopathy in wholemount mucosal-submucosal biopsies [12]
In conclusion, our study has produced results that are less than definitive but it suggests that the tested immunohistochemical methods are not adequate for the prediction of PD in endoscopically obtained gastroinestinal biopsies
Summary
Since the discovery of aggregated and phosphorylated alpha-synuclein as the primary component of Lewy pathology, immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis of Parkinson’s disease (PD) [1, 2]. The aim of our research project was to test several different immunohistochemical methods for the detection of LTS in colonic biopsy with the objective of identifying a highly sensitive and specific technique that might be widely and readily used in different laboratories. For this purpose, a panel of expert investigators have participated, based on their published work using alpha-synuclein immunohistochemistry [2, 13, 18, 19] and were asked to stain identical sets of paraffin-embedded sections from colonic biopsies with their own optimized method
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