Evidence map›Paper›PMID 26582899›Full record

ArticleScience translational medicine2015

The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis.

Jinkuk Choi, Jie Gao, Jaekwang Kim, Cynthia Hong, Jungsu Kim, Peter Tontonoz

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 21% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  5. Deletion of neuronal Idol ameliorates Alzheimer's disease-related pathologies via APOE receptors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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  14. Deletion ofScience advances · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Jinkuk ChoiHoward Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jie GaoHoward Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jaekwang KimDepartment of Neuroscience, Mayo Graduate School, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
Cynthia HongHoward Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jungsu KimDepartment of Neuroscience, Mayo Graduate School, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA. ptontonoz@mednet.ucla.edu kim.jungsu@mayo.edu.
Peter TontonozHoward Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. ptontonoz@mednet.ucla.edu kim.jungsu@mayo.edu.
Howard Hughes Medical Institute · USUniversity of California, Los Angeles · US

Funding

NUCLEAR RECEPTOR SIGNALING PATHWAYS IN ATHEROGENESISR01HL066088 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2001 to 2018
$5.4M
Translational Neuroscientist and the Hope CenterP30NS069329 · NINDS · WASHINGTON UNIVERSITY · PI GOATE, ALISON M · 2009 to 2010
$1.4M
The Idol-ApoE receptor pathway in Alzheimer's diseaseK99AG054736 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GAO, JIE · 2017 to 2018
$193k
Howard Hughes Medical InstituteNHLBI NIH HHS HL066088NHLBI NIH HHS R01 HL066088NIA NIH HHS K99 AG054736NINDS NIH HHS NS069329NINDS NIH HHS P30 NS069329
6 · The paper itself

Abstract

Apolipoprotein E (ApoE) is an important modifier of Alzheimer's disease (AD) pathogenesis, and its abundance has been linked to the clearance of β-amyloid (Aβ) in the brain. The pathways that control the clearance of ApoE in the brain are incompletely understood. We report that Idol, an E3 ubiquitin ligase that targets the low-density lipoprotein receptor (LDLR) for degradation, is a critical determinant of brain ApoE metabolism and Aβ plaque biogenesis. Previous work has shown that Idol contributes minimally to the regulation of hepatic LDLR expression in mice. By contrast, we demonstrate that Idol is a primary physiological regulator of LDLR protein in the brain, controlling the clearance of both ApoE-containing high-density lipoprotein (HDL) particles and Aβ. We studied the consequences of loss of Idol expression in a transgenic mouse model of Aβ amyloidosis. Idol deficiency increased brain LDLR, decreased ApoE, decreased soluble and insoluble Aβ, reduced amyloid plaque burden, and ameliorated neuroinflammation. These findings identify Idol as a gatekeeper of LDLR-dependent ApoE and Aβ clearance in the brain and a potential enzyme target for therapeutic intervention in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloidosisAnimalsApolipoproteins EBrainCell LineDisease Models, AnimalFemaleGenetic Predisposition to DiseaseMaleMice, Inbred C57BLMice, KnockoutPhenotypePlaque, AmyloidProteolysisAmyloid beta-PeptidesApolipoproteins EMylip protein, mouseReceptors, LDLUbiquitin-Protein Ligases

Identifiers

PMID26582899
PMCPMC7153735
OpenAlexW2177820706

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.