Evidence map›Paper›PMID 40393454›Full record

ArticleImmunity2025

Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease.

Priya Prakash, Palak Manchanda, Evi Paouri, Kanchan Bisht, Kaushik Sharma, Jitika Rajpoot, Victoria Wendt, Ahad Hossain, Prageeth R Wijewardhane, Caitlin E Randolph and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing 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

81 citing papers in PubMed.

  1. Lipophagy and lipid droplets in neurodegeneration.Trends in pharmacological sciences · 2026
    Review
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  10. When myelin breaks, tau aggregates - a new perspective on Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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  20. Heterogeneity, dynamics and organelle interactions of lipid droplets.Nature reviews. Molecular cell biology · 2026
    Review

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Priya PrakashDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Palak ManchandaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Evi PaouriDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Kanchan BishtDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Kaushik SharmaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Jitika RajpootDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Victoria WendtDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Ahad HossainDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Prageeth R WijewardhaneDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Caitlin E RandolphDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Yihao ChenDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Sarah StankoDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Nadia GasmiDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Anxhela GjojdeshiDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Sophie CardDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Jonathan FineDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Krupal P JethavaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Matthew G ClarkDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Bin DongDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Seohee MaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Alexis CrockettDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Elizabeth A ThayerDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Marlo NicolasDivision of Pathology, Cleveland Clinic, Cleveland, OH 44106, USA.
Ryann DavisDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Dhruv HardikarDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Daniela AllendeDivision of Pathology, Cleveland Clinic, Cleveland, OH 44106, USA.
Richard A PraysonDivision of Pathology, Cleveland Clinic, Cleveland, OH 44106, USA.
Chi ZhangDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Dimitrios DavalosDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: davalod@ccf.org.
Gaurav ChopraDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA; Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA. Electronic address: gchopra@purdue.edu.

Funding

Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI ANDREW D MESECAR · 1985 to 2026
$43.4M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Project Two - Exercise Training Decreases Alcohol Drinking by an FGF21-Dependent MechanismP50AA024333 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2016 to 2026
$19.6M
Pericyte control of capillary perfusion in the Alzheimer's disease brainR01AG081840 · NIA · SEATTLE CHILDREN'S HOSPITAL · PI Andy Y Shih · 2023 to 2026
$3.4M
Gliovascular Mechanisms of Blood-Brain Barrier Disruption in Neuroinflammatory DiseaseR01NS112526 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI DAVALOS, DIMITRIOS · 2019 to 2023
$2.4M
Development of a high throughput system for molecular imaging of different cell types in mouse brain tissuesRF1MH128866 · NIMH · PURDUE UNIVERSITY · PI CHOPRA, GAURAV, LASKIN, JULIA · 2021 to 2021
$1.5M
Chemical instruments-aware distributed blockchain based open AI platform to accelerate drug discoveryU18TR004146 · NCATS · PURDUE UNIVERSITY · PI CHOPRA, GAURAV, JAYACHANDRAN, GUHA · 2022 to 2023
$1.1M
NCATS NIH HHS U18 TR004146NCATS NIH HHS UL1 TR002529NCI NIH HHS P30 CA023168NIAAA NIH HHS P50 AA024333NIA NIH HHS R01 AG081840NIMH NIH HHS RF1 MH128866NINDS NIH HHS R01 NS112526
6 · The paper itself

Abstract

Microglial phagocytosis genes have been linked to increased risk for Alzheimer's disease (AD), but the mechanisms translating genetic association to cellular dysfunction remain unknown. Here, we showed that microglia formed lipid droplets (LDs) upon amyloid-β (Aβ) exposure and that LD loads increased with proximity to amyloid plaques in brains from individuals with AD and the 5xFAD mouse model. LD-laden microglia exhibited defects in Aβ phagocytosis, and unbiased lipidomic analyses identified a parallel decrease in free fatty acids (FFAs) and increase in triacylglycerols (TGs) as the key metabolic transition underlying LD formation. Diacylglycerol O-acyltransferase 2 (DGAT2)-a key enzyme that converts FFAs to TGs-promoted microglial LD formation and was increased in mouse 5xFAD and human AD brains. Pharmacologically targeting DGAT2 improved microglial uptake of Aβ and reduced plaque load and neuronal damage in 5xFAD mice. These findings identify a lipid-mediated mechanism underlying microglial dysfunction that could become a therapeutic target for AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesDiacylglycerol O-AcyltransferaseLipid DropletsMicrogliaAnimalsBrainDisease Models, AnimalHumansMaleMiceMice, TransgenicPhagocytosisPlaque, AmyloidTriglyceridesAmyloid beta-PeptidesDGAT2 protein, humanDGAT2 protein, mouseDiacylglycerol O-AcyltransferaseTriglyceridesAlzheimer’s diseaseamyloidDGAT2lipid dropletslipidomicslipidsmetabolismmicroglianeurodegenerationphagocytosis

Identifiers

PMID40393454
PMCPMC12168635

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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.