Evidence map›Paper›PMID 33232556›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2021

Immunohistochemical Detection of Synuclein Pathology in Skin in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinsonism.

Ahmed Al-Qassabi, Tsu-Shuen Tsao, Adriana Racolta, Thomas Kremer, Marta Cañamero, Anton Belousov, Madison A Santana, Rachel C Beck, Hongjun Zhang, Jeffrey Meridew and 12 more

Open access · greenAbstract read
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 3 pooled it
3.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.

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  18. Skin nerve phosphorylated α-synuclein in the elderly.Journal of neuropathology and experimental neurology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 5 countries.

Ahmed Al-QassabiDepartment of Neurology, McGill University-Montreal General Hospital, Montreal, Quebec, Canada.ORCID 0000-0003-0019-8793
Tsu-Shuen TsaoRoche Tissue Diagnostics, Tucson, Arizona, USA.
Adriana RacoltaRoche Tissue Diagnostics, Tucson, Arizona, USA.
Thomas KremerRoche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Marta CañameroRoche Pharmaceutical Research and Early Development, Penzberg, Germany.
Anton BelousovRoche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Madison A SantanaRoche Tissue Diagnostics, Tucson, Arizona, USA.
Rachel C BeckRoche Tissue Diagnostics, Tucson, Arizona, USA.
Hongjun ZhangRoche Tissue Diagnostics, Tucson, Arizona, USA.
Jeffrey MeridewRoche Tissue Diagnostics, Tucson, Arizona, USA.
Judith PughRoche Tissue Diagnostics, Tucson, Arizona, USA.
Fangru LianRoche Tissue Diagnostics, Tucson, Arizona, USA.
Mark D RobidaRoche Tissue Diagnostics, Tucson, Arizona, USA.
Mirko RitterRoche Centralised and Point of Care Solutions, Penzberg, Germany.
Christian CzechRoche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Thomas G BeachBanner Sun Health Research Institute, Sun City, Arizona, USA.
Lidija Pestic-DragovichRoche Tissue Diagnostics, Tucson, Arizona, USA.
Kirsten I TaylorRoche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Wagner ZagoProthena Biosciences Inc., South San Francisco, California, USA.
Lei TangRoche Tissue Diagnostics, Tucson, Arizona, USA.
Sebastian DziadekRoche Pharmaceutical Research and Early Development, Roche Innovation Centre Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Ronald B PostumaDepartment of Neurology, McGill University-Montreal General Hospital, Montreal, Quebec, Canada.
Roche (United States) · USRoche (Switzerland) · CHMontreal General Hospital · CABanner Sun Health Research Institute · USProthena (United States) · USRoche Pharma AG (Germany) · DE

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI Nicholas Ashton · 2021 to 2026
$24.9M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072980NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

backgroundRecent studies reported abnormal alpha-synuclein deposition in biopsy-accessible sites of the peripheral nervous system in Parkinson's disease (PD). This has considerable implications for clinical diagnosis. Moreover, if deposition occurs early, it may enable tissue diagnosis of prodromal PD.

objectiveThe aim of this study was to develop and test an automated bright-field immunohistochemical assay of cutaneous pathological alpha-synuclein deposition in patients with idiopathic rapid eye movement sleep behavior disorder, PD, and atypical parkinsonism and in control subjects.

methodsFor assay development, postmortem skin biopsies were taken from 28 patients with autopsy-confirmed Lewy body disease and 23 control subjects. Biopsies were stained for pathological alpha-synuclein in automated stainers using a novel dual-immunohistochemical assay for serine 129-phosphorylated alpha-synuclein and pan-neuronal marker protein gene product 9.5. After validation, single 3-mm punch skin biopsies were taken from the cervical 8 paravertebral area from 79 subjects (28 idiopathic rapid eye movement sleep behavior disorder, 20 PD, 10 atypical parkinsonism, and 21 control subjects). Raters blinded to clinical diagnosis assessed the biopsies.

resultsThe immunohistochemistry assay differentiated alpha-synuclein pathology from nonpathological-appearing alpha-synuclein using combined phosphatase and protease treatments. Among autopsy samples, 26 of 28 Lewy body samples and none of the 23 controls were positive. Among living subjects, punch biopsies were positive in 23 (82%) subjects with idiopathic rapid eye movement sleep behavior disorder, 14 (70%) subjects with PD, 2 (20%) subjects with atypical parkinsonism, and none (0%) of the control subjects. After a 3-year follow-up, eight idiopathic rapid eye movement sleep behavior disorder subjects phenoconverted to defined neurodegenerative syndromes, in accordance with baseline biopsy results.

conclusionEven with a single 3-mm punch biopsy, there is considerable promise for using pathological alpha-synuclein deposition in skin to diagnose both clinical and prodromal PD. © 2020 International Parkinson and Movement Disorder Society.

Indexed as

Lewy Body DiseaseParkinson DiseaseREM Sleep Behavior Disorderalpha-SynucleinHumansSkinalpha-Synucleinalpha-synucleinParkinson's diseasePGP9.5RBDskin biopsyUCHL1

Identifiers

PMID33232556
PMCPMC10123546
OpenAlexW3109944840

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.