Evidence map›Paper›PMID 42367943›Full record

ArticlebioRxiv : the preprint server for biology2026

APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.

Rachel Ee, Meelad Amouzgar, Jumana Afaghani, Kausalia Vijayaragavan, Bryan J Cannon, Dunja Mrdjen, Dmitry Tebaykin, Angie Spence, Cathrine Sant, David Aley and 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. 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

22 authors.

Rachel EeDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0009-0004-9597-4760
Meelad AmouzgarDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0521-9223
Jumana AfaghaniDepartment of Pathology, Stanford University, Stanford, CA, USA.
Kausalia VijayaragavanDepartment of Pathology, Stanford University, Stanford, CA, USA.
Bryan J CannonDepartment of Pathology, Stanford University, Stanford, CA, USA.
Dunja MrdjenDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-9269-2806
Dmitry TebaykinDepartment of Pathology, Stanford University, Stanford, CA, USA.
Angie SpenceDepartment of Pathology, Stanford University, Stanford, CA, USA.
Cathrine SantGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
David AleyGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Zhongyi GuoGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Kamilla SedovDepartment of Pathology, Stanford University, Stanford, CA, USA.
Faria ZafarDepartment of Pathology, Stanford University, Stanford, CA, USA.
Kathleen S MontineDepartment of Pathology, Stanford University, Stanford, CA, USA.
Amalia PernaDepartment of Pathology, Stanford University, Stanford, CA, USA.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, AZ, USA.ORCID 0000-0002-9527-2011
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
Michael AngeloDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-1531-5067
Birgitt SchüleDepartment of Pathology, Stanford University, Stanford, CA, USA.
M Ryan CorcesGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
Thomas J MontineDepartment of Pathology, Stanford University, Stanford, CA, USA.
Sean C BendallDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-1341-2453

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Wnt signaling in muscle stem cell agingP01AG036695 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARGARET A. GOODELL · 2011 to 2026
$29.3M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI ALIREZA ATRI · 2021 to 2026
$24.9M
Project 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, MUCKE, LENNART · 2021 to 2025
$23.4M
Stanford Cancer Immune Monitoring and Analysis Center (CIMAC)U24CA224309 · NCI · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Holden T. Maecker · 2017 to 2026
$19.9M
Project 4: Novel reagent development to enable molecular characterizationU19AG065156 · NIA · UNIVERSITY OF WASHINGTON · PI TIAN, LU · 2020 to 2024
$15.9M
Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologiesU01AG072573 · NIA · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL, MONTGOMERY, STEPHEN · 2021 to 2025
$8.3M
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
The Bone Marrow Multi-modal Imaging CoreU54HL165445 · NHLBI · STANFORD UNIVERSITY · PI ANGELO, ROBERT MICHAEL, BENDALL, SEAN CURTIS · 2022 to 2025
$5.9M
MIRIAD - Multiplexed Imaging of Resilience In Alzheimers DiseaseR01AG057915 · NIA · STANFORD UNIVERSITY · PI ANGELO, ROBERT MICHAEL, BENDALL, SEAN CURTIS · 2017 to 2021
$4.5M
NCI NIH HHS R01 CA240638NCI NIH HHS R01 CA251858NCI NIH HHS U24 CA224309NHLBI NIH HHS U54 HL165445NIAID NIH HHS T32 AI007290NIA NIH HHS P01 AG036695NIA NIH HHS P01 AG073082NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG072980NIA NIH HHS R01 AG056287NIA NIH HHS R01 AG057915NIA NIH HHS R01 AG068279NIA NIH HHS R01 AG078702NIA NIH HHS R01 AG088656NIA NIH HHS U01 AG072573NIA NIH HHS U19 AG065156NINDS NIH HHS R01 NS121404NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

Variation in APOE, notably the ε4 allele, profoundly shapes risk and severity of late-onset Alzheimer's disease (AD), yet how it remodels human microglial states remains unresolved. We combine spatially resolved proteomic profiling with single-nuclear multiomic analyses to define microglial organization across APOE3/3 and APOE4/4 genotypes in AD. Quantifying condition-associated variation across the cellular manifold reveals a continuous landscape of microglial states. APOE4/4 shifts cells toward terminal states marked by loss of homeostatic identity, metabolic disruption, and incomplete acquisition of disease-associated programs. We identify an APOE4/4-enriched population in AD that exhibits inflammatory signaling without effective metabolic or phagocytic engagement, localizing to niches of gliosis and senescence, and coupled to chronic stress adaptation programs. Together with evidence that APOE4/4 potentiates the activation threshold of nascent microglia, these findings establish a unified framework for human microglial state change, linking genetic risk to spatial and molecular organization of immune responses in the AD brain.

Identifiers

PMID42367943
PMCPMC13308055

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.