ArticleNature communications2020
Multiscale causal networks identify VGF as a key regulator of Alzheimer's disease.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 3 pooled it
12.2field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
115 citing papers in PubMed, 3 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Could VGF and/or its derived peptide act as biomarkers for the diagnosis of neurodegenerative diseases: A systematic review.Frontiers in endocrinology · 2022Pooled it
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age.Nature communications · 2019Pooled it
- Efficient differential expression analysis of large-scale single-cell transcriptomics data using Dreamlet.Nature communications · 2026Article
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Multilayer Proteome and Metabolome-Based Validation Uncovers Combined Regulatory Roles and Predictive Values of 6 RNA Modifications and Cellular Senescence in Alzheimer's Disease.CNS neuroscience & therapeutics · 2026Article
- Mapping cross-domain drivers of Alzheimer's disease risk through integrated network analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons.Aging cell · 2026Article
- A transcriptional program associated with neurotransmission in the living human brain.Molecular psychiatry · 2026Article
- PSEN1 mutant marmoset fibroblasts mimic multi-omic signatures of Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Top-Down Mass Spectrometry and Its Current Applications in Biomarker Discovery in Aging and Age-Related Diseases.International journal of molecular sciences · 2026Review
- Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity.Cell reports · 2026Article
- Article
- Golgi Fragmentation as a Potential Link Between SARS-CoV-2 Infection and Alzheimer's Disease: Mechanisms and Implications for Neurodegeneration in Long COVID.Sub-cellular biochemistry · 2026Review
- Associations of cerebrospinal fluid measures of synaptic function with white matter microstructure and cognition in older adults.Frontiers in aging neuroscience · 2026Article
- A study of gene expression in the living human brain.Molecular psychiatry · 2026Article
- Identifying transcriptomic signatures that mediate the causal effect of genotype on Alzheimer's disease.Frontiers in neuroscience · 2026Article
- Airway transcriptome networks for ozone and PMGenome medicine · 2025Article
- Cognitive resilience in preclinical Alzheimer's disease: Higher NPTX2 and VGF levels are associated with reduced cognitive decline.Neurobiology of aging · 2025Article
- Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer's Disease.Research square · 2025Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 5 institutions in 2 countries.
Noam D Beckmann *Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Wei-Jye Lin *Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120, Guangzhou, China.
Minghui Wang *Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-9171-4962
Ariella T CohainDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Alexander W CharneyDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Pei WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-6890-6453
Weiping MaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Ying-Chih WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Cheng JiangGraduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-4583-3295
Mickael AudrainNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-9941-7380
Phillip H ComellaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Amanda K FakiraNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Siddharth P HariharanNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0003-1814-6457
Gillian M BelbinDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Kiran GirdharDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Allan I LeveyDepartment of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-3153-502X
Nicholas T SeyfriedDepartment of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-4507-624X
Eric B DammerDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-2947-7606
Duc DuongDepartment of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA.
James J LahDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Jean-Vianney Haure-MirandeDepartment of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-5748-9666
Ben ShackletonDepartment of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Tomas FanutzaDepartment of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-2563-9121
Robert BlitzerDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Eimear KennyDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Jun ZhuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0003-0834-8178
Vahram HaroutunianNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-5860-2512
Pavel KatselDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Sam GandyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Zhidong TuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Michelle E EhrlichDepartment of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Stephen R SaltonNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. stephen.salton@mssm.edu.ORCID http://orcid.org/0000-0003-4087-8427
Eric E SchadtDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA. eric.schadt@mssm.edu.ORCID http://orcid.org/0000-0002-7892-8808
Icahn School of Medicine at Mount Sinai · USAllen Institute for Brain Science · USEmory University · USJames J. Peters VA Medical Center · USSema4 (United States) · US
Funding
Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Margaret Sewell · 2020 to 2026
$31.0MIntegrative 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
$26.0MThe Emory Alzheimer's Disease CenterP50AG025688 · NIA · EMORY UNIVERSITY · PI WINGO, THOMAS SPURGEON · 2005 to 2019
$25.7MDiscovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4MENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2008 to 2018
$6.8MIntegrative 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
$6.3MValidation of Antibody Reagents for 15 High Priority AMP-AD TargetsRF1AG057443 · NIA · SAGE BIONETWORKS · PI BRENNAN , PAUL, MANGRAVITE, LARA M · 2017 to 2019
$6.0MSystems modeling of shared and distinct molecular mechanisms underlying comorbid Major Depressive Disorder and Alzheimer's diseaseR01AG062355 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, SALTON, STEPHEN R · 2018 to 2022
$4.7MSystems Biology based Proteogenomic Translator for Cancer Marker Discovery towards Precision MedicineU24CA210993 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHADT, ERIC E, WANG, PEI · 2016 to 2020
$4.6MMolecular 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
$4.2MSYSTEMATIC 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
$4.2MVGF peptide TLQP-21, a novel microglial C3aR1 modulator in Alzheimer's diseaseRF1AG062661 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, SALTON, STEPHEN R · 2019 to 2019
$4.1MNCI NIH HHS U24 CA210993NIA NIH HHS P30 AG066514NIA NIH HHS P50 AG025688NIA NIH HHS R01 AG053960NIA NIH HHS R01 AG055501NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG062355NIA NIH HHS R01 AG067312NIA NIH HHS RF1 AG054014NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057443NIA NIH HHS RF1 AG059319NIA NIH HHS RF1 AG062661NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG046170NIDA NIH HHS HHSN271201300031CNIDDK NIH HHS R01 DK117504NIMH NIH HHS R01 MH086499NIMH NIH HHS R21 MH083496NIMH NIH HHS R33 MH083496NINDS NIH HHS P30 NS055077
Abstract
Though discovered over 100 years ago, the molecular foundation of sporadic Alzheimer's disease (AD) remains elusive. To better characterize the complex nature of AD, we constructed multiscale causal networks on a large human AD multi-omics dataset, integrating clinical features of AD, DNA variation, and gene- and protein-expression. These probabilistic causal models enabled detection, prioritization and replication of high-confidence master regulators of AD-associated networks, including the top predicted regulator, VGF. Overexpression of neuropeptide precursor VGF in 5xFAD mice partially rescued beta-amyloid-mediated memory impairment and neuropathology. Molecular validation of network predictions downstream of VGF was also achieved in this AD model, with significant enrichment for homologous genes identified as differentially expressed in 5xFAD brains overexpressing VGF. Our findings support a causal role for VGF in protecting against AD pathogenesis and progression.
Indexed as
Protein Interaction MapsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDatasets as TopicDisease Models, AnimalFemaleGene Expression ProfilingGene Regulatory NetworksGenome-Wide Association StudyHumansMaleMiceAmyloid beta-PeptidesNerve Growth FactorsVGF protein, humanVgf protein, mouse
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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.