Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?

In recent years, several studies have investigated the potential of immunohistochemical detection of α‐synuclein in the gastrointestinal tract to diagnose Parkinson's disease (PD). Although methodological heterogeneity has hindered comparability between studies, it has become increasingly appar...

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Main Authors: Ruffmann, Claudio, Parkkinen, Laura
Format: Online
Language:English
Published: John Wiley and Sons Inc. 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755164/
id pubmed-4755164
recordtype oai_dc
spelling pubmed-47551642016-02-25 Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making? Ruffmann, Claudio Parkkinen, Laura Reviews In recent years, several studies have investigated the potential of immunohistochemical detection of α‐synuclein in the gastrointestinal tract to diagnose Parkinson's disease (PD). Although methodological heterogeneity has hindered comparability between studies, it has become increasingly apparent that the high sensitivity and specificity reported in preliminary studies has not been sustained in subsequent large‐scale studies. What constitutes pathological α‐synuclein in the alimentary canal that could distinguish between PD patients and controls and how this can be reliably detected represent key outstanding questions in the field. In this review, we will comment on and compare the variable technical aspects from previous studies, and by highlighting some advantages and shortcomings we hope to delineate a standardized approach to facilitate the consensus criteria urgently needed in the field. Furthermore, we will describe alternative detection techniques to conventional immunohistochemistry that have recently emerged and may facilitate ease of interpretation and reliability of gastrointestinal α‐synuclein detection. Such techniques have the potential to detect the presence of pathological α‐synuclein and include the paraffin‐embedded tissue blot, the proximity ligation assay, the protein misfolding cyclic amplification technique, and the real‐time quaking‐induced conversion assay. Finally, we will review 2 nonsynonymous theories that have driven enteric α‐synuclein research, namely, (1) that α‐synuclein propagates in a prion‐like fashion from the peripheral nervous system to the brain via vagal connections and (2) that gastrointestinal α‐synuclein deposition may be used as a clinically useful biomarker in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. John Wiley and Sons Inc. 2016-01-22 2016-02 /pmc/articles/PMC4755164/ /pubmed/26799450 http://dx.doi.org/10.1002/mds.26480 Text en © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ruffmann, Claudio
Parkkinen, Laura
spellingShingle Ruffmann, Claudio
Parkkinen, Laura
Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
author_facet Ruffmann, Claudio
Parkkinen, Laura
author_sort Ruffmann, Claudio
title Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
title_short Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
title_full Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
title_fullStr Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
title_full_unstemmed Gut Feelings About α‐Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
title_sort gut feelings about α‐synuclein in gastrointestinal biopsies: biomarker in the making?
description In recent years, several studies have investigated the potential of immunohistochemical detection of α‐synuclein in the gastrointestinal tract to diagnose Parkinson's disease (PD). Although methodological heterogeneity has hindered comparability between studies, it has become increasingly apparent that the high sensitivity and specificity reported in preliminary studies has not been sustained in subsequent large‐scale studies. What constitutes pathological α‐synuclein in the alimentary canal that could distinguish between PD patients and controls and how this can be reliably detected represent key outstanding questions in the field. In this review, we will comment on and compare the variable technical aspects from previous studies, and by highlighting some advantages and shortcomings we hope to delineate a standardized approach to facilitate the consensus criteria urgently needed in the field. Furthermore, we will describe alternative detection techniques to conventional immunohistochemistry that have recently emerged and may facilitate ease of interpretation and reliability of gastrointestinal α‐synuclein detection. Such techniques have the potential to detect the presence of pathological α‐synuclein and include the paraffin‐embedded tissue blot, the proximity ligation assay, the protein misfolding cyclic amplification technique, and the real‐time quaking‐induced conversion assay. Finally, we will review 2 nonsynonymous theories that have driven enteric α‐synuclein research, namely, (1) that α‐synuclein propagates in a prion‐like fashion from the peripheral nervous system to the brain via vagal connections and (2) that gastrointestinal α‐synuclein deposition may be used as a clinically useful biomarker in PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
publisher John Wiley and Sons Inc.
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755164/
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