Evidence map›Paper›PMID 39698934›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain.

Benjamin P Readhead, Diego F Mastroeni, Qi Wang, Maria A Sierra, Camila de Ávila, Tajudeen O Jimoh, Jean-Vianney Haure-Mirande, Kristina E Atanasoff, Jennifer Nolz, Crystal Suazo and 31 more

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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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

41 authors.

Benjamin P ReadheadASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Diego F MastroeniASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Qi WangASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Maria A SierraDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.
Camila de ÁvilaASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Tajudeen O JimohDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jean-Vianney Haure-MirandeDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kristina E AtanasoffDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jennifer NolzASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Crystal SuazoASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Nathaniel J BartonDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Adrian R OrszulakDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Samantha M ChigasDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Khanh TranDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Anne MirzaDepartment of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Krista RyonDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.
Jacqueline ProszynskiDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.
Deena NajjarDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.
Joel T DudleyASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, Arizona, USA.
Sean T H LiuDivision of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Sam GandyDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Michelle E EhrlichDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Eric AlsopDivision of Neurogenomics, The Translational Genomics Research Institute, Phoenix, Arizona, USA.
Jerry AntoneDivision of Neurogenomics, The Translational Genomics Research Institute, Phoenix, Arizona, USA.
Rebecca ReimanDivision of Neurogenomics, The Translational Genomics Research Institute, Phoenix, Arizona, USA.
Cory FunkInstitute for Systems Biology, Seattle, Washington, USA.
Rebecca L BestSerimmune, Inc, Goleta, California, USA.
Michael JhatroSerimmune, Inc, Goleta, California, USA.
Kathy KamathSerimmune, Inc, Goleta, California, USA.
John ShonSerimmune, Inc, Goleta, California, USA.
Timothy F KowalikDepartment of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Winnie S LiangDivision of Neurogenomics, The Translational Genomics Research Institute, Phoenix, Arizona, USA.
Geidy E SerranoCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
Thomas G BeachCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
Kendall Van Keuren-JensenDivision of Neurogenomics, The Translational Genomics Research Institute, Phoenix, Arizona, USA.
Christopher E MasonDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, New York, USA.
Yingleong ChanDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Elaine T LimDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Domenico TortorellaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Eric M ReimanBanner Alzheimer's Institute, Phoenix, Arizona, USA.

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI ALIREZA ATRI · 2021 to 2026
$24.9M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
Identification of the genetic and transcriptomic networks of cognitive and neuropathological resilience to Alzheimer's Disease associated virusesU01AG061835 · NIA · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI READHEAD, BENJAMIN · 2018 to 2022
$6.5M
Integrated understanding of complex viral network biology in Alzheimer's DiseaseRF1AG058469 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI EHRLICH, MICHELLE E, GANDY, SAMUEL E. · 2019 to 2019
$4.1M
Transcriptomics-based identification of cell type specific host genes and gene networks perturbed by HSV-1 in cerebral organoids.R01AG083881 · NIA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Teng-Ting Elaine Lim · 2024 to 2026
$2.5M
Examining the effect of cadmium metal exposure on Alzheimer's disease genetic alleles using herpes viral infected cerebral organoidsU01AG088673 · NIA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Ying Leong Chan · 2024 to 2026
$2.5M
Integrated understanding of complex viral network biology in Alzheimer's DiseaseR56AG058469 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DUDLEY, JOEL THOMAS, EHRLICH, MICHELLE E · 2017 to 2017
$844k
Investigation of chromosomally integrated Human Herpesvirus 6 as a risk factor for Alzheimer's diseaseR21AG063068 · NIA · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI READHEAD, BENJAMIN · 2019 to 2020
$467k
Arizona Alzheimer's ConsortiumBenter FoundationGlobal Lyme AllianceNIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072980NIA NIH HHS P30 AG19610NIA NIH HHS R01AG058469NIA NIH HHS R01 AG083881NIA NIH HHS R01AG083881NIA NIH HHS R21 AG063068NIA NIH HHS R21AG063068NIA NIH HHS R56 AG058469NIA NIH HHS RF1 AG058469NIA NIH HHS U01 AG061835NIA NIH HHS U01AG061835NIA NIH HHS U01 AG088673NIH HHS U01AG088673NINDS NIH HHS U24 NS072026NOMIS Stiftung
6 · The paper itself

Abstract

introductionWhile there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

methodsWe used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

resultsCD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death. DISCUSSION: Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+) microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+) microglia. HIGHLIGHTS: Cross-tissue interaction between HCMV and the adaptive immune response in a subset of persons with AD. Presence of CD83(+) microglial associated with IgG4 and HCMV in the gut. CD83(+) microglia are also associated presence of HCMV and IgG4 in the cortex and vagal nerve. Replication of key association in an independent cohort of AD subjects. HCMV infection of cerebral organoids accelerates the production of AD neuropathological features.

Indexed as

Alzheimer DiseaseAntigens, CDBrainCytomegalovirusImmunoglobulin GImmunoglobulinsMembrane GlycoproteinsMicrogliaVagus NerveAgedAged, 80 and overCD83 AntigenCytomegalovirus InfectionsFemaleHumansMaleAntigens, CDCD83 AntigenImmunoglobulin GImmunoglobulinsMembrane GlycoproteinsAlzheimer's diseaseantibody epitope repertoire analysisCD83(+) microgliacerebrospinal fluidhuman cytomegalovirusimmunoglobulin G4immunohistochemistryprefrontal cortexsuperior frontal gyrustransverse colonvagus nerveviral infection

Identifiers

PMID39698934
PMCPMC11772737

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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 OpenQuestion graph.