Evidence map›Paper›PMID 29636460›Full record

ArticleTranslational psychiatry2018

CXCR4 involvement in neurodegenerative diseases.

Luke W Bonham, Celeste M Karch, Chun C Fan, Chin Tan, Ethan G Geier, Yunpeng Wang, Natalie Wen, Iris J Broce, Yi Li, Matthew J Barkovich and 18 more

Open access · goldAbstract read
In one paragraph

Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Systematic review and meta-analysis of bulk RNAseq studies in human Alzheimer's disease brain tissue.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
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  17. IL-1β and CXCR4 as Potential Therapeutic Targets for Alzheimer's Disease.Combinatorial chemistry & high throughput screening · 2025
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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

28 authors at 10 institutions in 4 countries.

Luke W BonhamDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Celeste M KarchDepartment of Psychiatry, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6854-5547
Chun C FanDepartment of Cognitive Sciences, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9437-2128
Chin TanDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0980-9936
Ethan G GeierDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Yunpeng WangNORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0001-9831-1090
Natalie WenDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Iris J BroceDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.
Yi LiDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.
Matthew J BarkovichDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8257-423X
Raffaele FerrariDepartment of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
John HardyDepartment of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
Parastoo MomeniDepartment of Internal Medicine, Laboratory of Neurogenetics, Texas Tech University Health Science Center, Lubbock, TX, USA.
Günter HöglingerDepartment of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.ORCID http://orcid.org/0000-0001-7587-6187
Ulrich MüllerInstitut for Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
Christopher P HessDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.
Leo P SugrueDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.
William P DillonDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Bruce L MillerDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Ole A AndreassenNORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0002-4461-3568
Anders M DaleDepartment of Cognitive Sciences, University of California, San Diego, La Jolla, CA, USA.
A James BarkovichDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA.
Jennifer S YokoyamaDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Rahul S DesikanDepartment of Radiology and Biomedical Imaging, Neuroradiology Section, University of California, San Francisco, San Francisco, CA, USA. rahul.desikan@ucsf.edu.
International FTD-Genomics Consortium (IFGC)
International Parkinson’s Disease Genetics Consortium (IPDGC)
International Genomics of Alzheimer’s Project (IGAP)
University of California, San Francisco · USUniversity of Pennsylvania · USUniversity College London · GBWashington University in St. Louis · USUniversity of California San Diego · USGerman Center for Neurodegenerative Diseases · DEOslo University Hospital · NOTexas Tech University · USGenomics (United Kingdom) · GBJustus-Liebig-Universität Gießen · DE

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
RNA signatures of frontotemporal dementia and ALS due to C9ORF72 expansionK01AG049152 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2015 to 2019
$648k
GENETIC DISRUPTION OF TAU METABOLISM IN TAUOPATHIESK01AG046374 · NIA · WASHINGTON UNIVERSITY · PI KARCH, CELESTE MARIE · 2014 to 2018
$568k
Medical Research Council G0301152Medical Research Council G0400074Medical Research Council G0502157Medical Research Council G0900652Medical Research Council G1100540Medical Research Council MC_U105597119Medical Research Council MC_U123160657Medical Research Council MC_UU_00005/12Medical Research Council MC_UU_00024/1Medical Research Council MC_UU_00024/9NIA NIH HHS K01 AG046374NIA NIH HHS K01 AG049152NIA NIH HHS P01 AG003991NIA NIH HHS P50 AG005681
6 · The paper itself

Abstract

Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a 'network' of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.

Indexed as

Genetic Predisposition to DiseaseAnimalsBrainGene ExpressionGene Regulatory NetworksGenome-Wide Association StudyHumansMice, TransgenicMicrogliaNeurodegenerative DiseasesPolymorphism, Single NucleotideReceptors, CXCR4Risk FactorsCXCR4 protein, humanReceptors, CXCR4

Identifiers

PMID29636460
PMCPMC5893558
OpenAlexW2751698792

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.