Evidence map›Paper›PMID 40696045›Full record

ArticleNature immunology2025

Spatial proteomics of Alzheimer's disease-specific human microglial states.

Dunja Mrdjen, Bryan J Cannon, Meelad Amouzgar, YeEun Kim, Candace Liu, Kausalia Vijayaragavan, Christine Camacho, Angie Spence, Erin F McCaffrey, Anusha Bharadwaj and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature immunology, 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.

  1. Pooled it
  2. Review
  3. Article
  4. Microglia-targetedMaterials today. Bio · 2026
    Article
  5. Emerging technologies in the spatial proteomics landscape.Analytical and bioanalytical chemistry · 2026
    Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Dunja Mrdjen *Department of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Bryan J Cannon *Department of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Meelad AmouzgarDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-0521-9223
YeEun KimDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-3347-183X
Candace LiuDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Kausalia VijayaragavanDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Christine CamachoDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-4924-591X
Angie SpenceDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Erin F McCaffreyDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Anusha BharadwajDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Dmitry TebaykinDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-0913-8834
Syed BukhariDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Marc BosseDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-4912-8059
Felix J HartmannDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0002-4174-2276
Adam KagelDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
John Paul OliveriaDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Koya YakabiDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, AZ, USA.
Maria M CorradaDepartment of Neurology, University of California, Irvine, CA, USA.
Claudia H KawasDepartment of Neurology, University of California, Irvine, CA, USA.
Robert TibshiraniDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
M Ryan CorcesGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7465-7652
Will GreenleafDepartment of Genetics, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-1409-3095
R Michael AngeloDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-1531-5067
Thomas MontineDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA. tmontine@stanford.edu.ORCID http://orcid.org/0000-0002-1346-2728
Sean C BendallDepartment of Pathology, Stanford University, School of Medicine, Palo Alto, CA, USA. bendall@stanford.edu.ORCID http://orcid.org/0000-0003-1341-2453

Funding

Wnt signaling in muscle stem cell agingP01AG036695 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARGARET A. GOODELL · 2011 to 2026
$29.3M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Stanford Cancer Immune Monitoring and Analysis Center (CIMAC)U24CA224309 · NCI · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Holden T. Maecker · 2017 to 2026
$19.9M
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
Uncovering mechanisms of protection from Alzheimer's disease in CHIP using human cohorts and biosamplesR01AG088656 · NIA · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Siddhartha Jaiswal · 2024 to 2026
$4.3M
Deciphering the Glycan Code in Human Alzheimer’s Disease BrainR01AG078702 · NIA · UNIVERSITY OF KENTUCKY · PI Peggi M Angel, Sean Curtis Bendall · 2022 to 2026
$3.8M
The Phenotypic Landscape of Cognitive Decline as Revealed by Next-Generation Multiplexed Ion Beam ImagingR01AG056287 · NIA · STANFORD UNIVERSITY · PI ANGELO, ROBERT MICHAEL, BENDALL, SEAN CURTIS · 2017 to 2021
$2.6M
Uncoupling Age- Versus Cognitive-Related Cellular Senescence in Alzheimer's DiseaseR01AG068279 · NIA · STANFORD UNIVERSITY · PI BENDALL, SEAN CURTIS · 2020 to 2024
$1.9M
NCI NIH HHS U24 CA224309NHLBI NIH HHS U54 HL165445NIAID NIH HHS T32 AI007290NIA NIH HHS P01 AG036695NIA NIH HHS R01 AG056287NIA NIH HHS R01 AG057915NIA NIH HHS R01 AG068279NIA NIH HHS R01 AG078702NIA NIH HHS R01 AG088656
6 · The paper itself

Abstract

Microglia are implicated in aging, neurodegeneration and Alzheimer's disease (AD). Low-plex protein imaging does not capture cellular states and interactions in the human brain, which differs from rodent models. Here we used multiplexed ion beam imaging to spatially map cellular states and niches in cognitively normal human brains, identifying a spectrum of proteomic microglial profiles. Defined by immune activation states that were skewed across brain regions and compartmentalized according to microenvironments, this spectrum enables the identification of proteomic trends across the microglia of ten cognitively normal individuals and orthogonally with single-nuclei epigenetic analysis, revealing associated molecular functions. Notably, AD tissues exhibit regulatory shifts in the immunologically active cells at the end of the proteomic spectrum, including enrichment of CD33 and CD44 and decreases in HLA-DR, P2RY12 and ApoE expression. These findings establish an in situ, single-cell spatial proteomic framework for AD-specific microglial states.

Indexed as

Alzheimer DiseaseBrainMicrogliaProteomeProteomicsAgedAged, 80 and overApolipoproteins EFemaleHLA-DR AntigensHumansHyaluronan ReceptorsMaleSialic Acid Binding Ig-like Lectin 3Single-Cell AnalysisApolipoproteins ECD33 protein, humanCD44 protein, humanHLA-DR AntigensHyaluronan ReceptorsProteomeSialic Acid Binding Ig-like Lectin 3

Identifiers

PMID40696045
PMCPMC13075585

What Socratic 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 Socratic graph.