Evidence map›Paper›PMID 28241068›Full record

ArticlePloS one2017

Liver X receptor agonist treatment significantly affects phenotype and transcriptome of APOE3 and APOE4 Abca1 haplo-deficient mice.

Alexis Y Carter, Florent Letronne, Nicholas F Fitz, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Valerie L Reeves, Hafsa Kamboh, Iliya Lefterov, Radosveta Koldamova

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 23 citations in OpenAlex.

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  9. Apolipoprotein E in lipid metabolism and neurodegenerative disease.Trends in endocrinology and metabolism: TEM · 2023
    Review
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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

10 authors at 1 institution in 1 country.

Alexis Y CarterDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Florent LetronneDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Nicholas F FitzDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Anais MounierDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Cody M WolfeDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Kyong Nyon NamDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Valerie L ReevesDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Hafsa KambohDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
Iliya LefterovDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-0249-0280
Radosveta KoldamovaDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA.
University of Pittsburgh · US

Funding

Epigenetic and phenotypic effects of arsenic: impacts on cognition and ADR01ES024233 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KOLDAMOVA, RADOSVETA, LEFTEROV, ILIYA · 2014 to 2018
$2.6M
Genome wide analysis of LXR binding - metabolic and epigenetic regulation in ADR01AG037919 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEFTEROV, ILIYA, SCHUG, JONATHAN · 2012 to 2016
$2.4M
LXR and human ApoE isoform effects on AD phenotype: in vitro and in vivo modelsR01AG037481 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KOLDAMOVA, RADOSVETA · 2011 to 2015
$1.8M
Peripheral & Brain Cholesterol Metabolism in Neurodegenerative Mouse ModelsK01AG044490 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FITZ, NICHOLAS FRANCIS · 2014 to 2018
$463k
NIA NIH HHS K01 AG044490NIA NIH HHS R01 AG037481NIA NIH HHS R01 AG037919NIEHS NIH HHS R01 ES024233
6 · The paper itself

Abstract

ATP-binding cassette transporter A1 (ABCA1) controls cholesterol and phospholipid efflux to lipid-poor apolipoprotein E (APOE) and is transcriptionally controlled by Liver X receptors (LXRs) and Retinoic X Receptors (RXRs). In APP transgenic mice, lack of Abca1 increased Aβ deposition and cognitive deficits. Abca1 haplo-deficiency in mice expressing human APOE isoforms, increased level of Aβ oligomers and worsened memory deficits, preferentially in APOE4 mice. In contrast upregulation of Abca1 by LXR/RXR agonists significantly ameliorated pathological phenotype of those mice. The goal of this study was to examine the effect of LXR agonist T0901317 (T0) on the phenotype and brain transcriptome of APP/E3 and APP/E4 Abca1 haplo-deficient (APP/E3/Abca1+/- and APP/E4/Abca1+/-) mice. Our data demonstrate that activated LXRs/RXR ameliorated APOE4-driven pathological phenotype and significantly affected brain transcriptome. We show that in mice expressing either APOE isoform, T0 treatment increased mRNA level of genes known to affect brain APOE lipidation such as Abca1 and Abcg1. In both APP/E3/Abca1+/- and APP/E4/Abca1+/- mice, the application of LXR agonist significantly increased ABCA1 protein level accompanied by an increased APOE lipidation, and was associated with restoration of APOE4 cognitive deficits, reduced levels of Aβ oligomers, but unchanged amyloid load. Finally, using Gene set enrichment analysis we show a significant APOE isoform specific response to LXR agonist treatment: Gene Ontology categories "Microtubule Based Process" and "Synapse Organization" were differentially affected in T0-treated APP/E4/Abca1+/- mice. Altogether, the results are suggesting that treatment of APP/E4/Abca1+/- mice with LXR agonist T0 ameliorates APOE4-induced AD-like pathology and therefore targeting the LXR-ABCA1-APOE regulatory axis could be effective as a potential therapeutic approach in AD patients, carriers of APOEε4.

Indexed as

TranscriptomeAmyloid beta-PeptidesAnimalsApolipoprotein E3Apolipoprotein E4ATP Binding Cassette Transporter 1Behavior, AnimalBrainCluster AnalysisFearFemaleHaploinsufficiencyHeterozygoteHumansLiver X ReceptorsMaleABCA1 protein, humanAbca1 protein, mouseAmyloid beta-PeptidesApolipoprotein E3Apolipoprotein E4ATP Binding Cassette Transporter 1Liver X Receptors

Identifiers

PMID28241068
PMCPMC5328633
OpenAlexW2594697404

What OpenQuestion holds

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LicenceCC BY
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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.