Evidence map›Paper›PMID 30577786›Full record

ArticleActa neuropathologica communications2018

GJA1 (connexin43) is a key regulator of Alzheimer's disease pathogenesis.

Yuji Kajiwara, Erming Wang, Minghui Wang, Wun Chey Sin, Kristen J Brennand, Eric Schadt, Christian C Naus, Joseph Buxbaum, Bin Zhang

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 2 pooled it
3.2field-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

63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.

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  16. Risk of Alzheimer's disease in Down syndrome: Insights gained by multi-omics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
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  18. Article
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3 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 2 countries.

Yuji KajiwaraDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Erming WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Wun Chey SinDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Kristen J BrennandDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Eric SchadtDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Christian C NausDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Joseph BuxbaumDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. bin.zhang@mssm.edu.
Icahn School of Medicine at Mount Sinai · USUniversity of British Columbia · CA

Funding

Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WANG, MINGHUI, ZHANG, BIN · 2013 to 2022
$26.0M
Integrative Network Modeling of Cognitive Resilience to Alzheimer's DiseaseR01AG057907 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, HAROUTUNIAN, VAHRAM · 2017 to 2021
$6.3M
Molecular Characterization and Validation of Gender Differences in Alzheimers Disease PathogenesisRF1AG054014 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CAI, DONGMING, ZHANG, BIN · 2016 to 2016
$4.2M
SYSTEMATIC DRUG REPURPOSING TARGETING IMMUNE ACTIVATION NETWORKS IN ALZHEIMER'S DISEASE (AD)RF1AG059319 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2018 to 2018
$4.2M
Towards a comprehensive signaling pathway map of parahippocampal vulnerability in Alzheimers DiseaseRF1AG057440 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, NOGGLE, SCOTT ALLEN · 2017 to 2017
$3.5M
Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
NIA NIH HHS R01AG046170NIA NIH HHS R01 AG057907NIA NIH HHS R01AG057907NIA NIH HHS RF1 AG054014NIA NIH HHS RF1AG054014NIA NIH HHS RF1 AG057440NIA NIH HHS RF1AG057440NIA NIH HHS RF1 AG059319NIA NIH HHS U01 AG046170NIH HHS S10 OD018522
6 · The paper itself

Abstract

GJA1 (connexin43) has been predicted as the top key driver of an astrocyte enriched subnetwork associated with Alzheimer's disease (AD). In this study, we comprehensively examined GJA1 expression across 29 transcriptomic and proteomic datasets from post-mortem AD and normal control brains. We demonstrated that GJA1 was strongly associated with AD amyloid and tau pathologies and cognitive functions. RNA sequencing analysis of Gja1-/- astrocytes validated that Gja1 regulated the subnetwork identified in AD, and many genes involved in Aβ metabolism. Astrocytes lacking Gja1 showed reduced Apoe protein levels as well as impaired Aβ phagocytosis. Consistent with this, wildtype neurons co-cultured with Gja1-/- astrocytes contained higher levels of Aβ species than those with wildtype astrocytes. Moreover, Gja1-/- astrocytes was more neuroprotective under Aβ stress. Our results underscore the importance of GJA1 in AD pathogenesis and its potential for further investigation as a promising pharmacological target in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsAnimals, NewbornApolipoproteins EAstrocytesBrainCells, CulturedCohort StudiesConnexin 43CytokinesFemaleGene Expression RegulationGene Regulatory NetworksHumansMaleAmyloid beta-Peptidesamyloid beta-protein (1-42)Apolipoproteins EConnexin 43CytokinesGJA1 protein, humanPeptide FragmentsAlzheimer’s diseaseamyloidβAstrocyteconnexin43Cx43Gene networksGJA1

Identifiers

PMID30577786
PMCPMC6303945
OpenAlexW2905763822

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.