ArticleCell stem cell2025
Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model.
Abstract read
In one paragraph
Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
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
29 citing papers in PubMed.
- Review
- A collaborative framework for uncovering molecular and cellular drivers of VCID: Foundations for future interventions in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Is there a role for apolipoprotein E in perinatal brain injury?Molecular and cellular pediatrics · 2026Review
- Microglia-Neuron Crosstalk: An Intimate Molecular Conversation in Neurodegeneration.International journal of molecular sciences · 2026Review
- The 3xTg-AD Mouse Model: A Comprehensive Tool for Understanding Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- Altered Microglia-Neuron Crosstalk and Regional Heterogeneity in Alzheimer's Disease Revealed by Single-Nucleus RNA Sequencing.International journal of molecular sciences · 2026Article
- Neuroimmune Interactions in Neurodegeneration: The Role of Microglia in Alzheimer's and Parkinson's Disease Pathogenesis.Brain sciences · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- IL-34 in neurological homeostasis and its multifaceted roles in central nervous system diseases.Frontiers in immunology · 2026Review
- Neuronal APOE4 drives damaging lipid accumulation via contact-dependent neuron-oligodendrocyte-microglia interaction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic VEGFC treatment provides protection against traumatic-brain-injury-driven tauopathy pathogenesis.Cell reports · 2025Article
- Research progress of single cell RNA sequencing in nervous system.Molecular biology reports · 2025Review
- Microglia-to-neuron signaling linksProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Microglia-to-neuron signaling increases lipid droplet metabolism, enhancing neuronal network activity.bioRxiv : the preprint server for biology · 2025Article
- Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies.Neuron · 2025Review
- Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative Diseases and Targeted Therapy.Molecular neurobiology · 2025Review
- Variable and interactive effects of Sex, APOE ε4 and TREM2 on the deposition of tau in entorhinal and neocortical regions.Nature communications · 2025Article
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
Corrections and comments
- Update of
Authors and funding
16 authors.
Antara RaoGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Nuo ChenGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Gladstone Center for Translational Advancement, Gladstone Institutes, San Francisco, CA, USA.
Min Joo KimGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Jessica BlumenfeldGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Oscar YipGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Zherui LiangGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
David ShostakGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Yanxia HaoGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Gladstone Center for Translational Advancement, Gladstone Institutes, San Francisco, CA, USA.
Maxine R NelsonGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Nicole KoutsodendrisGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Brian GroneGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Gladstone Center for Translational Advancement, Gladstone Institutes, San Francisco, CA, USA.
Leo DingGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Gladstone Center for Translational Advancement, Gladstone Institutes, San Francisco, CA, USA.
Seo Yeon YoonGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Patrick ArriolaGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Misha ZilberterGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Yadong HuangGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Gladstone Center for Translational Advancement, Gladstone Institutes, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: yadong.huang@gladstone.ucsf.edu.
Funding
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6MProject 4: Cross-species Dissection of Cellular Response to APOE Genotype and AD Pathology Using Single-cell Multi-omicsP01AG073082 · NIA · J. DAVID GLADSTONE INSTITUTES · PI HUANG, YADONG · 2021 to 2025
$23.4MPREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7MNeuronal ApoE Drives Selective Neurodegeneration in Alzheimer's DiseaseR01AG071697 · NIA · J. DAVID GLADSTONE INSTITUTES · PI HUANG, YADONG · 2021 to 2025
$4.1MStudy the Protective Roles of ApoE2 in Alzheimer's Disease Using Reprogrammed Isogenic CellsR01AG065540 · NIA · J. DAVID GLADSTONE INSTITUTES · PI HUANG, YADONG · 2020 to 2024
$3.6MPredoctoral Training in NeurobiologyT32NS115706 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAMUEL JEREMY PLEASURE · 2020 to 2026
$3.4MApolipoprotein E4-related Electrophysiological and Metabolic Impairments in Aging and Alzheimer's DiseaseR01AG061150 · NIA · J. DAVID GLADSTONE INSTITUTES · PI ZILBERTER, MISHA YURI · 2019 to 2023
$3.3MStudy Susceptibility and Resistance to ApoE4 in Alzheimer's DiseaseRF1AG076647 · NIA · J. DAVID GLADSTONE INSTITUTES · PI HUANG, YADONG · 2022 to 2022
$2.6MStudy Susceptibility and Resistance to ApoE4 in Alzheimer's DiseaseR01AG076647 · NIA · J. DAVID GLADSTONE INSTITUTES · PI YADONG HUANG · 2025 to 2026
$1.7MBD FACSAria II Flow CytometerS10RR028962 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI CAVROIS, MARIELLE · 2011 to 2011
$544kStudy the Underlying Mechanisms of an Alzheimer’s-Disease-Protective ApoE MutationF31AG074690 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NELSON, MAXINE · 2021 to 2022
$78kCellular Source-Dependent Effects of ApoE4 on Tau Pathology in Alzheimer's DiseaseF31AG074672 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOUTSODENDRIS, NICOLE · 2021 to 2022
$78kNCRR NIH HHS S10 RR028962NIAID NIH HHS P30 AI027763NIA NIH HHS F31 AG074672NIA NIH HHS F31 AG074690NIA NIH HHS P01 AG073082NIA NIH HHS R01 AG061150NIA NIH HHS R01 AG065540NIA NIH HHS R01 AG071697NIA NIH HHS R01 AG076647NIA NIH HHS RF1 AG076647NICHD NIH HHS T32 HD007470NINDS NIH HHS T32 NS115706
Abstract
Despite strong evidence supporting the important roles of both apolipoprotein E4 (APOE4) and microglia in Alzheimer's disease (AD) pathogenesis, the effects of microglia on neuronal APOE4-related AD pathogenesis remain elusive. To examine such effects, we utilized microglial depletion in a chimeric model with induced pluripotent stem cell (iPSC)-derived human neurons in mouse hippocampus. Specifically, we transplanted homozygous APOE4, isogenic APOE3, and APOE-knockout (APOE-KO) iPSC-derived human neurons into the hippocampus of human APOE3 or APOE4 knockin mice and then depleted microglia in half of the chimeric mice. We found that both neuronal APOE and microglial presence were important for the formation of Aβ and tau pathologies in an APOE isoform-dependent manner (APOE4 > APOE3). Single-cell RNA sequencing analysis identified two pro-inflammatory microglial subtypes with elevated MHC-II gene expression enriched in chimeric mice with human APOE4 neuron transplants. These findings highlight the concerted roles of neuronal APOE, especially APOE4, and microglia in AD pathogenesis.
Indexed as
Alzheimer DiseaseApolipoprotein E4Disease Models, AnimalInduced Pluripotent Stem CellsMicrogliaNeuronsAnimalsChimeraHippocampusHumansMiceApolipoprotein E4Alzheimer’s diseaseamyloidAPOE4chimeric disease modeliPSCmicrogliaRNA-seqtautransplantation
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.