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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Auteurs principaux: Ruffmann, C, Parkkinen, L
Format: Journal article
Langue:English
Publié: Wiley 2016
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author Ruffmann, C
Parkkinen, L
author_facet Ruffmann, C
Parkkinen, L
author_sort Ruffmann, C
collection OXFORD
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.
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spelling oxford-uuid:c2c025fa-4d52-4ee0-ae47-fd93a9e04f362022-03-27T06:11:09ZGut feelings about α-synuclein in gastrointestinal biopsies: biomarker in the making?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c2c025fa-4d52-4ee0-ae47-fd93a9e04f36EnglishSymplectic Elements at OxfordWiley2016Ruffmann, CParkkinen, LIn 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.
spellingShingle Ruffmann, C
Parkkinen, L
Gut feelings about α-synuclein in gastrointestinal biopsies: biomarker in the making?
title 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_short 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
work_keys_str_mv AT ruffmannc gutfeelingsaboutasynucleiningastrointestinalbiopsiesbiomarkerinthemaking
AT parkkinenl gutfeelingsaboutasynucleiningastrointestinalbiopsiesbiomarkerinthemaking