Evidence map›Paper›PMID 41928507›Full record

ArticleNeuron2026

Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer's disease models.

Byungwook Kim, Mason Douglas Tate, Hande Karahan, H R Sagara Wijeratne, Ahmad Daniel Sharify, Selena S Wang, Justin R Kim, Md Mamun Al-Amin, Kelly Hartigan, Sunwoo Chung and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  2. Review
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

16 authors.

Byungwook KimDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Mason Douglas TateDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Medical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hande KarahanDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
H R Sagara WijeratneDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Ahmad Daniel SharifyDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Selena S WangDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Justin R KimDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Md Mamun Al-AminDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Kelly HartiganDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Medical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Sunwoo ChungDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Luke Child DabinDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Dominic J AcriDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Emma H DoudDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Sutha K JohnDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Amber L MosleyDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Jungsu KimDepartment of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Medical Neuroscience Graduate Program, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: jk123@iu.edu.

Funding

The role of ABI3 in Alzheimers diseaseR01AG071281 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI KIM, JUNGSU · 2021 to 2025
$3.7M
Molecular genetic analyses of transcriptional dysregulation in Alzheimers diseaseR01AG077829 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Jungsu Kim · 2022 to 2026
$3.6M
Training Grant on Alzheimer's Disease and ADRD at Indiana UniversityT32AG071444 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI GARY E. LANDRETH, Bruce T Lamb · 2021 to 2026
$2.8M
The role of ABI3 in Alzheimers diseaseRF1AG074543 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI KIM, JUNGSU · 2021 to 2021
$2.3M
Generation of Abi3 conditional knockout mouse modelR21AG072738 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI KIM, JUNGSU · 2021 to 2021
$432k
Proteomic and functional analysis of missense variants of APOE associated with Alzheimer disease riskF30AG079580 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI WIJERATNE, HR SAGARA · 2022 to 2025
$159k
The role of micro-RNA-33 in Tau pathologyF31AG074673 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI TATE, MASON DOUGLAS · 2022 to 2023
$89k
NIA NIH HHS F30 AG079580NIA NIH HHS F31 AG074673NIA NIH HHS R01 AG071281NIA NIH HHS R01 AG077829NIA NIH HHS R21 AG072738NIA NIH HHS RF1 AG074543NIA NIH HHS T32 AG071444
6 · The paper itself

Abstract

Recent human genetic studies have highlighted the potential role of microglial genes and their regulatory functions in the pathogenesis of Alzheimer's disease (AD). The transcription factor PU.1 (encoded by SPI1) is expressed mainly in microglia in the central nervous system and has been reported to be a genetic risk factor for AD. However, the role of microglial SPI1 in AD etiology is still poorly understood. Here, we demonstrate that the selective deletion of Spi1 in microglia exacerbates AD-related pathologies in an amyloid mouse model. Specifically, microglial Spi1 deletion increases amyloid deposition, gliosis, and dystrophic neurites while decreasing the microglial response to plaques. By combining proteomics and functional analyses, we reveal that the loss of microglial Spi1 impairs phagocytosis through Syk, Lyn, and Fcgr1. Furthermore, directly activating these genes rescues the impaired amyloid-beta (Aβ) uptake caused by Spi1 knockdown, unveiling the potential mechanism of SPI1 in amyloid pathology.

Indexed as

Alzheimer DiseaseMicrogliaPlaque, AmyloidProto-Oncogene ProteinsTrans-ActivatorsAmyloid beta-PeptidesAnimalsDisease Models, AnimalMiceMice, TransgenicPhagocytosisProto-Oncogene Protein Spi-1Amyloid beta-PeptidesProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-ActivatorsAlzheimer’s diseaseamyloidamyloidosisFcgr1LynmicrogliaphagocytosisPU.1SPI1Syk

Identifiers

PMID41928507
PMCPMC13051965

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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.