Dataset Information

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4).

ABSTRACT: Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images.

SUBMITTER: Beach TG

PROVIDER: S-EPMC6097838 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4).

Beach Thomas G TG Serrano Geidy E GE Kremer Thomas T Canamero Marta M Dziadek Sebastian S Sade Hadassah H Derkinderen Pascal P Corbillé Anne-Gaëlle AG Letournel Franck F Munoz David G DG White Charles L CL Schneider Julie J Crary John F JF Sue Lucia I LI Adler Charles H CH Glass Michael J MJ Intorcia Anthony J AJ Walker Jessica E JE Foroud Tatiana T Coffey Christopher S CS Ecklund Dixie D Riss Holly H Goßmann Jennifer J König Fatima F Kopil Catherine M CM Arnedo Vanessa V Riley Lindsey L Linder Carly C Dave Kuldip D KD Jennings Danna D Seibyl John J Mollenhauer Brit B Chahine Lana L

Journal of neuropathology and experimental neurology 20180901 9

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-deriv ...[more]

PMID: 30107604

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Project description:PurposeTo assess the immunohistochemical and histopathological changes in a subject with Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC).DesignCase study.ParticipantNinety two year-old Caucasian male with ADVIRC.MethodsThe subject was documented clinically for 54 Years. The retina/choroid complex of the right eye was evaluated with cryosections stained with hematoxylin and eosin or periodic acid schiff reagent. Cryosections were also evaluated with immunofluorescence or alkaline phosphatase immunohistochemistry (IHC) using primary antibodies against bestrophin1, GFAP, PEDF, RPE65, TGFβ, VEGF, and vimentin. The left retina and choroid were evaluated as flat mounts using immunofluorescence. UEA lectin was used to stain viable vasculature.Main outcome measuresThe immunohistochemical and histopathological changes in retina and choroid from a subject with ADVIRC.ResultsThe subject had a heterozygous c.248G>A variant in exon 4 of the BEST1 gene. There was widespread chorioretinal degeneration and atrophy except for an island of spared RPE monolayer in the perimacula/macula OU. In this region, some photoreceptors were present, choriocapillaris was spared, and retinal pigment epithelial cells were in their normal disposition. There was a Muller cell periretinal membrane throughout much of the fundus. Bestrophin-1 was not detected or only minimally present by IHC in the ADVIRC RPE, even in the spared RPE area. Beyond the island of retained RPE monolayer on Bruch's membrane (BrMb), there was migration of RPE into the neuro-retina, often ensheathing blood vessels and producing excessive matrix within their perivascular aggregations.ConclusionsThe primary defect in ADVIRC is in RPE, the only cells in the eye that express the BEST1 gene. The dysfunctional RPE cells may go through epithelial/mesenchymal transition as they migrate from BrMb to form papillary aggregations in the neuro-retina, often ensheathing blood vessels. This may be the reason for retinal blood vessel nonperfusion. Migration of RPE from BrMb was also associated with attenuation of the choriocapillaris.

Dataset Information

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4).

Publications

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4).

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