Evidence map›Paper›PMID 41546868›Full record

ArticleCell reports2026

Inducible deletion of DGAT1 and 2 from microglia exacerbates neurodegeneration and endolysosomal lipid accumulation in male PS19 mice.

G Travis Tabor, Alexandra Litvinchuk, Yun Chen, Austin Allison, Elizabeth W Sun, Bettina van Lengerich, Sonnet S Davis, Elizabeth West, Johannes C M Schlachetzki, Carisa Zeng and 27 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Lipophagy and lipid droplets in neurodegeneration.Trends in pharmacological sciences · 2026
    Review
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  5. Article
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

37 authors.

G Travis TaborDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA; Medical Scientist Training Program, Washington University, St. Louis, MO, USA.
Alexandra LitvinchukDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Yun ChenDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Austin AllisonDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Elizabeth W SunTenvie Therapeutics, Inc., South San Francisco, CA, USA.
Bettina van LengerichDenali Therapeutics, Inc., South San Francisco, CA, USA.
Sonnet S DavisDenali Therapeutics, Inc., South San Francisco, CA, USA.
Elizabeth WestDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Johannes C M SchlachetzkiDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Carisa ZengDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.
Hao HuDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Peter B LinDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Prabal SharmaDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Xiaoying ChenLaboratory of System Neuroimmunology, Institute for Immunology, IDG/McGovern Institute for Brain Research, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Samira ParhizkarDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Sihui SongDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Xin BaoDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Lakshita SenthilUniversity of Chicago, Chicago, IL, USA.
Abhirami K IyerDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Shih Feng YouDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Javier Remolina SerranoDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Melissa ManisDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Emily FrankeDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
Anil G CashikarDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Carla M YuedeDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Jung H SuhDenali Therapeutics, Inc., South San Francisco, CA, USA.
Celeste M KarchDepartment of Psychiatry, Washington University, St. Louis, MO, USA.
Andrew FolickDepartment of Medicine, Division of Endocrinology and Metabolism, University of California, San Francisco, San Francisco CA, USA.
Suneil K KoliwadDepartment of Medicine, Division of Endocrinology and Metabolism, University of California, San Francisco, San Francisco CA, USA.
Robert V FareseCell Biology Program, Sloan Kettering Institute, New York, NY, USA.
Tobias WaltherCell Biology Program, Sloan Kettering Institute, New York, NY, USA; Howard Hughes Medical Institute, New York, NY, USA.
Eric J HuangDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.
Maxim ArtyomovDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Gilbert Di PaoloDenali Therapeutics, Inc., South San Francisco, CA, USA.
Jason D UlrichDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA.
David M HoltzmanDepartment of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, MO, USA. Electronic address: holtzman@wustl.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI Celeste Marie Karch · 2021 to 2026
$42.0M
Effect of APOE on CNS Neurons: Role of LRPRF1NS090934 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2020 to 2025
$6.5M
Perturbing the LXR/SREBP axis to decipher protective and pathogenic AD/ADRD microglial phenotypesRF1AG083977 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COUFAL, NICOLE GABRIELE, GLASS, CHRISTOPHER K · 2024 to 2024
$3.8M
Therapeutic Strategy to Treat Alzheimer's Disease by VGF Delivery into BrainR01AG083981 · NIA · NORTH DAKOTA STATE UNIVERSITY · PI Takahisa Kanekiyo, Jagdish Singh · 2023 to 2026
$2.4M
Nikon Confocal Microscope for Shared Biomedical ResearchS10OD030233 · OD · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2022 to 2022
$538k
WHOLE SLIDE IMAGING SYSTEM FOR TRANSLATIONAL NEUROSCIENCES10RR027552 · NCRR · WASHINGTON UNIVERSITY · PI LEE, JIN-MOO · 2010 to 2010
$275k
Elucidating roles of microglial lipid droplets in neurodegenerationF30AG081100 · NIA · WASHINGTON UNIVERSITY · PI TABOR, GEORGE TRAVIS · 2023 to 2025
$123k
NCI NIH HHS P30 CA008748NCRR NIH HHS S10 RR027552NIA NIH HHS F30 AG081100NIA NIH HHS R01 AG083981NIA NIH HHS RF1 AG083977NIA NIH HHS U19 AG069701NIH HHS S10 OD030233NINDS NIH HHS RF1 NS090934
6 · The paper itself

Abstract

Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipids are often assumed to be contained in lipid droplets (LDs). While studies have been performed in cell culture and Drosophila models to characterize glial LDs, the roles of microglial LD biogenesis in mammalian tauopathy are unclear. To address this issue, we induced the deletion of diacylglycerol acyltransferases (DGATs) 1 and 2, enzymes critical for LD formation, from microglia in the PS19 mouse model of tauopathy. Microglial DGAT double knockout (KO) exacerbated neurodegeneration and increased the abundance of brain cholesteryl esters in male PS19 mice. Myeloid cell lipid accumulations appeared to largely localize to endosomes/lysosomes, not LDs, at baseline and were exacerbated upon DGAT KO. Our results suggest that microglial DGAT-dependent TAG/LD biogenesis is adaptive in advanced tauopathy. Most lipid accumulation in brain myeloid cells does not appear to correspond to LDs in this tauopathy model, which has implications for the development of lipid-modulating therapies for neurodegenerative diseases.

Indexed as

Diacylglycerol O-AcyltransferaseEndosomesGene DeletionLipid MetabolismLysosomesMicrogliaNeurodegenerative DiseasesAnimalsBrainLipid DropletsMaleMiceMice, KnockoutDgat1 protein, mouseDGAT2 protein, mouseDiacylglycerol O-AcyltransferaseCD68cholesteryl esterCP: metabolismCP: neurosciencediacylglycerol acyltransferaselipid dropletlysosomemicroglianeurodegenerationPS19tauopathytriglyceride

Identifiers

PMID41546868
PMCPMC12951297

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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.