Evidence map›Paper›PMID 35687573›Full record

ArticlePloS one2022

Alpha-synuclein and tau are abundantly expressed in the ENS of the human appendix and monkey cecum.

Alexandra D Zinnen, Jonathan Vichich, Jeanette M Metzger, Julia C Gambardella, Viktoriya Bondarenko, Heather A Simmons, Marina E Emborg

Abstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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  5. Article
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

7 authors.

Alexandra D ZinnenWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Jonathan VichichWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Jeanette M MetzgerWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Julia C GambardellaWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Viktoriya BondarenkoWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Heather A SimmonsWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Marina E EmborgWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.ORCID 0000-0002-9351-6641

Funding

WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
Modeling Frontotemporal Dementia in Rhesus MacaquesR33NS115102 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI CHEN, RUI, EMBORG, MARINA · 2022 to 2024
$1.8M
NCI NIH HHS P30 CA014520NIH HHS P51 OD011106NINDS NIH HHS R33 NS115102
6 · The paper itself

Abstract

α-Synuclein (α-syn) proteinopathy in the neurons of the Enteric Nervous System (ENS) is proposed to have a critical role in Parkinson's disease (PD) onset and progression. Interestingly, the ENS of the human appendix harbors abundant α-syn and appendectomy has been linked to a decreased risk and delayed onset of PD, suggesting that the appendix may influence PD pathology. Common marmosets and rhesus macaques lack a distinct appendix (a narrow closed-end appendage with a distinct change in diameter at the junction with the cecum), yet the cecal microanatomy of these monkeys is similar to the human appendix. Sections of human appendix (n = 3) and ceca from common marmosets (n = 4) and rhesus macaques (n = 3) were evaluated to shed light on the microanatomy and the expression of PD-related proteins. Analysis confirmed that the human appendix and marmoset and rhesus ceca present thick walls comprised of serosa, muscularis externa, submucosa, and mucosa plus abundant lymphoid tissue. Across all three species, the myenteric plexus of the ENS was located within the muscularis externa with nerve fibers innervating all layers of the appendix/ceca. Expression of α-syn and tau in the appendix/cecum was present within myenteric ganglia and along nerve fibers of the muscularis externa and mucosa in all species. In the myenteric ganglia α-syn, p-α-syn, tau and p-tau immunoreactivities (ir) were not significantly different across species. The percent area above threshold of α-syn-ir and tau-ir in the nerve fibers of the muscularis externa and mucosa were greater in the human appendix than in the NHP ceca (α-syn-ir p<0.05; tau-ir p<0.05). Overall, this study provides critical translational evidence that the common marmoset and rhesus macaque ceca are remarkably similar to the human appendix and, thus, that these NHP species are suitable for studying the development of PD linked to α-syn and tau pathological changes in the ENS.

Indexed as

AppendixEnteric Nervous SystemParkinson Diseasealpha-SynucleinAnimalsHumansMacaca mulattatau Proteinsalpha-Synucleintau Proteins

Identifiers

PMID35687573
PMCPMC9187115

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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.