TY - JOUR
T1 - Multicenter Assessment of Immunohistochemical Methods for Pathological Alpha-Synuclein in Sigmoid Colon of Autopsied Parkinson's Disease and Control Subjects
AU - Beach, Thomas G.
AU - Corbillé, Anne Gaëlle
AU - Letournel, Franck
AU - Kordower, Jeffrey H.
AU - Kremer, Thomas
AU - Munoz, David G.
AU - Intorcia, Anthony
AU - Hentz, Joseph
AU - Adler, Charles H.
AU - Sue, Lucia I.
AU - Walker, Jessica
AU - Serrano, Geidy
AU - Derkinderen, Pascal
N1 - Funding Information:
This study was supported by a grant from the Michael J. Fox Foundation for Parkinson's Research (Grant ID: 9035.01). The Banner Sun Health Research Institute Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research. AGC is a recipient of a "poste d'accueil Inserm".
Publisher Copyright:
© 2016 - IOS Press and the authors. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Background: Conflicting results from studies of Lewy-type α-synucleinopathy (LTS) in colonic biopsies of subjects with Parkinson's disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4:35, 2016), examined archived colonic biopsies and found that none of the tested methods was adequately sensitive or specific. Objective: As the amount of nervous tissue in typical colonic biopsies may be insufficient, and the clinical diagnosis of PD not completely accurate, the objective of the current study was to use instead full-thickness sections of sigmoid colon from autopsy-proven PD and normal subjects. Methods: Seven different immunohistochemical (IHC) methods were used, employing five different primary antibodies and four different combinations of epitope exposure and signal development protocols. Specific staining was defined as being restricted to morphological features consistent with neuronal elements. Stained slides from each subject were independently categorized as being positive or negative for LTS, and their density semi-quantitatively graded, by four raters blinded to diagnosis. Results: Agreement and mean diagnostic performance varied markedly between raters. With the two most accurate raters, 5 methods achieved diagnostic accuracies of 70 or greater; one method had 100 accuracy and 100 inter-rater agreement. The submucosa had the highest prevalence of pathological LTS staining, followed by the muscularis and mucosa. Conclusions: The major conclusion of this study is that, when sufficient submucosa and LTS is present, and when specific staining is defined as being consistent with neuronal morphology, adequately-trained raters may reliably distinguish PD colon from control using suitable IHC methods.
AB - Background: Conflicting results from studies of Lewy-type α-synucleinopathy (LTS) in colonic biopsies of subjects with Parkinson's disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4:35, 2016), examined archived colonic biopsies and found that none of the tested methods was adequately sensitive or specific. Objective: As the amount of nervous tissue in typical colonic biopsies may be insufficient, and the clinical diagnosis of PD not completely accurate, the objective of the current study was to use instead full-thickness sections of sigmoid colon from autopsy-proven PD and normal subjects. Methods: Seven different immunohistochemical (IHC) methods were used, employing five different primary antibodies and four different combinations of epitope exposure and signal development protocols. Specific staining was defined as being restricted to morphological features consistent with neuronal elements. Stained slides from each subject were independently categorized as being positive or negative for LTS, and their density semi-quantitatively graded, by four raters blinded to diagnosis. Results: Agreement and mean diagnostic performance varied markedly between raters. With the two most accurate raters, 5 methods achieved diagnostic accuracies of 70 or greater; one method had 100 accuracy and 100 inter-rater agreement. The submucosa had the highest prevalence of pathological LTS staining, followed by the muscularis and mucosa. Conclusions: The major conclusion of this study is that, when sufficient submucosa and LTS is present, and when specific staining is defined as being consistent with neuronal morphology, adequately-trained raters may reliably distinguish PD colon from control using suitable IHC methods.
KW - Lewy body
KW - biopsy
KW - diagnosis
KW - enteric nervous system
KW - gastrointestinal tract
KW - pathology
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U2 - 10.3233/JPD-160888
DO - 10.3233/JPD-160888
M3 - Article
C2 - 27589538
AN - SCOPUS:84994113227
SN - 1877-7171
VL - 6
SP - 761
EP - 770
JO - Journal of Parkinson's Disease
JF - Journal of Parkinson's Disease
IS - 4
ER -