Evidence map›Paper›PMID 39210471›Full record

ArticleMolecular neurodegeneration2024

Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease.

Qiang Chen, Luis Aguirre, Guoming Liang, Huanhuan Zhao, Tao Dong, Felix Borrego, Itziar de Rojas, Qichan Hu, Christopher Reyes, Ling-Yan Su and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Qiang ChenLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Luis AguirreGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
Guoming LiangCollege of Animal Science, Shanxi Agricultural University, Taigu, Shanxi, China.
Huanhuan ZhaoBioinformatics Program, University of Texas at El Paso, El Paso, TX, USA.
Tao DongDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Felix BorregoGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
Itziar de RojasResearch Center and Memory Clinic, Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Qichan HuGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
Christopher ReyesGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
Ling-Yan SuCollege of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China.
Bao ZhangCollege of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
James D LechleiterDepartment of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Harald H H GöringSouth Texas Diabetes and Obesity Institute and Division of Human Genetics, University of Texas Rio Grande Valley School of Medicine, San Antonio, TX, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA.
Joel E KleinmanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Thomas M HydeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Pan P LiDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Agustín RuizGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
Daniel R WeinbergerLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Sudha SeshadriGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA. Seshadri@uthscsa.edu.
Liang MaGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA. mal1@uthscsa.edu.ORCID 0000-0001-7034-9011

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Exploring the Role of the Brain Epigenome: Cognitive Decline and Life ExperiencesR01AG036042 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2009 to 2013
$4.1M
THERAPEUTIC STRATEGIES FOR ALZHEIMER'S DISEASE BASED ON TREM2 BIOLOGYRF1AG059082 · NIA · WASHINGTON UNIVERSITY · PI COLONNA, MARCO · 2019 to 2019
$2.6M
NIH HHS P30AG010161NIH HHS P30AG072975NIH HHS R01AG015819NIH HHS R01AG017917NIH HHS R01AG036042NIH HHS RF1AG059082NIH HHS RF1AG57473NIH HHS U01AG46152NIH HHS U01AG61356
6 · The paper itself

Abstract

backgroundThe APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized.

methodsTo identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development.

resultsWe identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups.

conclusionThe novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology.

Indexed as

Alzheimer DiseaseApolipoproteins EPolymorphism, Single NucleotideAgedBrainDNA MethylationFemaleGenetic Predisposition to DiseaseHumansMaleApoE protein, humanApolipoproteins EAlzheimer’s diseaseAPOEPostmortem brainSNPTranscript

Identifiers

PMID39210471
PMCPMC11361112

What Socratic holds

Textmetadata
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 Socratic graph.