Evidence map›Paper›PMID 40654744›Full record

ArticlebioRxiv : the preprint server for biology2025

APOE genotype confers context-dependent neurovascular vulnerability in immune-vascularized human forebrain organoids.

Haohui Fang, Xiangyu Liao, C Korin Bullen, Ruoyan Pu, Hu Wang, Juliana Condoleo, Sueanne Chear, Xueyi Chen, Yanjun Zhang, Sonya Zhang and 11 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Haohui FangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Xiangyu LiaoNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
C Korin BullenDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ruoyan PuNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hu WangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Juliana CondoleoNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sueanne ChearNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Xueyi ChenCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yanjun ZhangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sonya ZhangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Da HuoNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kadia LissitNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Alina YangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kateri JarvisNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stewart NeifertNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yuejia HuangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
William BishaiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sanjay K JainCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0001-9620-7070
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0002-6459-0893
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jin-Chong XuNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0002-9519-9029

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3M
Parthanatos, AIF and PAAN-1 in Neuronal InjuryR37NS067525 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DAWSON, TED M., DAWSON, VALINA L. · 2015 to 2021
$5.3M
Preclinical modeling to study Tuberculous MeningitisR01AI145435 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$4.0M
ACE2-targeted PET radiotracers for investigating spatiotemporal distribution of SARS-CoV-2 organ injury and therapy response.R01AI161829 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DESAI, TEJAL A., FLAVELL, ROBERT RICHARD · 2021 to 2023
$2.4M
NIAID NIH HHS R01 AI145435NIAID NIH HHS R01 AI161829NIA NIH HHS P30 AG066507NINDS NIH HHS R37 NS067525
6 · The paper itself

Abstract

The APOE gene is a major genetic determinant of neurovascular and immune function, yet the mechanisms by which its isoforms modulate brain vulnerability to pathogenic stress remain incompletely understood. Here, we employ isogenic human iPSC-derived immune-vascularized-Forebrain Organoid-based Multicellular Assembled Cerebral Organoids (FORMA-COs)-to dissect isoform-specific responses to a clinically relevant viral challenge. We find that APOE2/2 and APOE4/4 FORMA-COs exhibit heightened viral RNA burden and distinct neuroinflammatory profiles compared to APOE3/3. Specifically, APOE4/4 promotes IL-1α and VEGFA induction, whereas APOE2/2 leads to elevated TNF-β and VEGFA protein accumulation, indicating divergent pathways of injury. Integrated transcriptomic analyses, combined with known and predicted APOE protein-protein interaction networks, reveal genotype-dependent enrichment of cytokine signaling, angiogenic remodeling, and immune dysregulation. In vivo validation using humanized mouse models corroborates APOE genotype-specific vascular remodeling, microglial activation, and oligodendrocyte perturbation. These findings demonstrate that APOE genotype confers context-specific susceptibility to neuroimmune and vascular injury, providing insight into genetic risk mechanisms underlying infection-related and neurodegenerative brain disorders.

Identifiers

PMID40654744
PMCPMC12248126

What OpenQuestion holds

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LicenceCC BY-NC
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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.