ArticleNeuron2018
Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.
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Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 402 papers, 5 of them syntheses that pooled it.
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402citing papers in PubMed, 5 pooled it
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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.
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Who cites it
402 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Herpes simplex virus 2 and dementia risk: a systematic review and meta-analysis.Frontiers in dementia · 2026Pooled it
- Human herpesvirus 6 (HHV-6) infection and risk of Alzheimer's disease: a systematic review and meta-analysis.BMC neurology · 2025Pooled it
- Systematic review with meta-analysis of active herpesvirus infections in patients with COVID-19: Old players on the new field.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2023Pooled it
- The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Manifestations of Alzheimer's disease genetic risk in the blood are evident in a multiomic analysis in healthy adults aged 18 to 90.Scientific reports · 2022Pooled it
- Hospital-treated infection associated with Alzheimer's disease pathology: underlying mechanisms.Molecular psychiatry · 2026Review
- Herpes simplex virus and kallikrein-related peptidases - a functional connection in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Interpreting Viral Associations in Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- Association of Herpes Simplex Virus Type-1 With Dementia Outcomes: Longitudinal Retrospective Cohort Study Using Real-World Electronic Health Record Data.JMIR formative research · 2026Article
- Cytomegalovirus-induced T cell responses accelerate Alzheimer's disease progression in mice.Brain : a journal of neurology · 2026Article
- Review
- Delayed Pathogenicity inMicroorganisms · 2026Article
- Chemokines in Alzheimer's Disease: Early Defence, Late Damage and the Impact of Sex and Infection.Basic & clinical pharmacology & toxicology · 2026Review
- miR155, triplicated in Down syndrome, regulates the development of neural stem cells and GABAergic interneurons in Alzheimer's disease mouse and human iPSC models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Varicella zoster virus and the central nervous system.Nature reviews. Microbiology · 2026Review
- Metatranscriptomic Reanalysis of Alzheimer's Brains Identifies Low-Biomass Microbial Signals Including Enrichment ofInternational journal of molecular sciences · 2026Article
- A positive association between phosphorylated Tau217 (pTau217) and neural correlations is prevented by human leukocyte antigen allele DRB1*13:01.Scientific reports · 2026Article
- HIF3A-mediated aberrant activation of TXNIP promotes Alzheimer's disease progression.Scientific reports · 2026Article
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
342 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors.
Ben ReadheadDepartments of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute of Genomic Sciences and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Institute for Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ 85287-5001, USA.
Jean-Vianney Haure-MirandeDepartment of Neurology, Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cory C FunkInstitute for Systems Biology, Seattle, WA, 98109-5263, USA.
Matthew A RichardsInstitute for Systems Biology, Seattle, WA, 98109-5263, USA.
Paul ShannonInstitute for Systems Biology, Seattle, WA, 98109-5263, USA.
Vahram HaroutunianDepartments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; James J. Peters VA Medical Center, 130 West Kingsbridge Road, New York, NY 10468, USA.
Mary SanoJames J. Peters VA Medical Center, 130 West Kingsbridge Road, New York, NY 10468, USA; Department of Psychiatry, Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Winnie S LiangArizona Alzheimer's Consortium, Phoenix, AZ 85014, USA; Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Noam D BeckmannDepartments of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute of Genomic Sciences and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nathan D PriceInstitute for Systems Biology, Seattle, WA, 98109-5263, USA.
Eric M ReimanArizona Alzheimer's Consortium, Phoenix, AZ 85014, USA; Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA; Department of Psychiatry, University of Arizona, Phoenix, AZ 85721, USA; Banner Alzheimer's Institute, Phoenix, AZ 85006, USA.
Eric E SchadtDepartments of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute of Genomic Sciences and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Sema4, Stamford, CT 06902, USA.
Michelle E EhrlichDepartments of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute of Genomic Sciences and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neurology, Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sam GandyDepartment of Neurology, Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; James J. Peters VA Medical Center, 130 West Kingsbridge Road, New York, NY 10468, USA; Department of Psychiatry, Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for NFL Neurological Care, Department of Neurology, New York, NY 10029, USA.
Joel T DudleyDepartments of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute of Genomic Sciences and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Institute for Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ 85287-5001, USA. Electronic address: joel.dudley@mssm.edu.
Funding
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Charles B Hall · 1985 to 2026
$73.9MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MSUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9MResearch Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5MIntegrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's DiseaseU01AG046170 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2013 to 2022
$26.0MIntegrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MTrainingU54EB020406 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2014 to 2018
$12.5MNIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG019610NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036836NIA NIH HHS R34 AG049649NIA NIH HHS R56 AG058469NIA NIH HHS RF1 AG015819NIA NIH HHS RF1 AG058469NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046170NIBIB NIH HHS U54 EB020406NINDS NIH HHS R01 NS080820NINDS NIH HHS U24 NS072026
Abstract
Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer's disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD.
Indexed as
Herpesvirus 6, HumanHerpesvirus 7, HumanAdaptor Proteins, Signal TransducingAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesBrainCase-Control StudiesClusterinCohort StudiesEncephalitis, ViralGene Expression ProfilingGene Regulatory NetworksGenomicsAdaptor Proteins, Signal TransducingAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAPBB2 protein, humanAPP protein, humanAspartic Acid EndopeptidasesBACE1 protein, humanBIN1 protein, humanCLU protein, humanClusterinMicroRNAsMirn155 microRNA, mouseMonomeric Clathrin Assembly ProteinsNuclear ProteinsPICALM protein, humanPresenilin-1PSEN1 protein, humanTumor Suppressor ProteinsAlzheimer's diseaseHHV-6AHHV-6BHHV-7human herpesvirusintegrative genomicsmultiscale networksnetwork biologyRoseolovirussystems biology
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