Evidence map›Paper›PMID 40471789›Full record

ArticleCell reports2025

Astrocyte induction of disease-associated microglia is suppressed by acute exposure to fAD neurons in human iPSC triple cultures.

Alexandra M Lish, Nancy Ashour, Richard V Pearse, Paige C Galle, Gwendolyn A Orme, Sarah E Heuer, Courtney R Benoit, Kellianne D Alexander, Elyssa F L Grogan, Gizem Terzioglu and 5 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–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

23 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  10. Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
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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

15 authors.

Alexandra M LishAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nancy AshourAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Richard V PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Paige C GalleAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Gwendolyn A OrmeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Sarah E HeuerAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Courtney R BenoitAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Kellianne D AlexanderAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elyssa F L GroganAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Gizem TerziogluAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Allegra ScarpaAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Andrew M SternAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nicholas SeyfriedDepartment of Biochemistry, Emory School of Medicine, Atlanta, GA, USA.
Vilas MenonCenter for Translational and Computational Neuroimmunology, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
Tracy L Young-PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: tpearse@bwh.harvard.edu.

Funding

Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway 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
$13.6M
Alzheimer variants: Propagation of shared functional changes across cellular networksU01AG072572 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DE JAGER, PHILIP L, ST GEORGE-HYSLOP, PETER HENRY · 2021 to 2025
$8.5M
Probing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7M
Deconstructing and modeling the single cell architecture of the Alzheimer brainRF1AG057473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2017 to 2018
$4.0M
Cell and Molecular Consequences of Alzheimer's Disease Genetic Variants on BBB Integrity and FunctionRF1NS117446 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2020 to 2020
$3.6M
Elucidating changes in astrocyte subpopulations associated with resistance to Alzheimers Disease pathology in multi-ethnic cohortsR01AG066831 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MENON, VILAS · 2020 to 2024
$3.3M
Establishment of a Human Microphysiological System to Elucidate Cellular Mechanisms Underlying Vulnerability to ADRF1NS142331 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2025 to 2025
$2.7M
Identifying cell type-specific autonomous and non-autonomous interactions in ADRF1AG072167 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MENON, VILAS, YOUNG-PEARSE, TRACY L · 2022 to 2022
$2.6M
Building Novel Predictive Networks for high-throughput, in-silico Key Driver Prioritization to Enhance Drug Target Discovery in AMP-AD and M2OVE-ADRF1AG057457 · NIA · UNIVERSITY OF ARIZONA · PI BRADSHAW, ELIZABETH M, CHANG, RUI · 2017 to 2019
$2.3M
Cell and Molecular Consequences of Alzheimer's Disease Genetic Variants on BBB Integrity and FunctionR01NS117446 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2024 to 2024
$909k
NIA NIH HHS R01 AG055909NIA NIH HHS R01 AG066831NIA NIH HHS RF1 AG057457NIA NIH HHS RF1 AG057473NIA NIH HHS RF1 AG072167NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG072572NINDS NIH HHS R01 NS117446NINDS NIH HHS RF1 NS117446NINDS NIH HHS RF1 NS142331
6 · The paper itself

Abstract

Advancements in human induced pluripotent stem cell (hiPSC) technology have enabled co-culture models for disease modeling in physiologically relevant systems. However, co-culturing protocols face challenges in usability and consistency. Here, we introduce a robust, reproducible hiPSC-derived co-culture system integrating astrocytes, neurons, and microglia. This model leverages cryopreserved cells, enabling co-cultures within 20 days post-thaw. Comparing monocultures and tricultures, we demonstrate how cell-cell interactions shape transcriptional and functional states across all three cell types. Neurons in triculture exhibit increased spine density and activity, while astrocytes and microglia show altered responses to proinflammatory stimulation. Surprisingly, the presence of astrocytes induces upregulation of disease-associated microglia (DAM) genes, including TREM2, SPP1, APOE, and GPNMB in microglia. Additionally, while familial Alzheimer's disease neurons induce a prototypical inflammatory response in microglia, the DAM signature is significantly dampened. Collectively, this study establishes a versatile human triculture model as a valuable resource for dissecting neuron-glia interactions and their role in neurodegenerative disease.

Indexed as

Alzheimer DiseaseAstrocytesInduced Pluripotent Stem CellsMicrogliaNeuronsCells, CulturedCoculture TechniquesHumansAlzheimer’s diseaseAPOEastrocytesCP: NeuroscienceCP: Stem cell researchdisease-associated microgliafADiPSCsmicroglial statesTREM2triculture

Identifiers

PMID40471789
PMCPMC12282607

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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.