Evidence map›Paper›PMID 37333071›Full record

ArticlebioRxiv : the preprint server for biology2024

Amyloid β Induces Lipid Droplet-Mediated Microglial Dysfunction 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

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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, 29 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 3 institutions in 1 country.

Priya PrakashDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Palak ManchandaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0001-6194-8282
Evi PaouriDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Kanchan BishtDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0002-2575-8913
Kaushik SharmaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0003-2316-4609
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.ORCID 0000-0002-9781-3053
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.
Nadia GasmiDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.ORCID 0000-0002-3694-333X
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 NicolasDepartment of Anatomic 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 AllendeDepartment of Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44106, USA.
Richard A PraysonDepartment of Anatomic 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.ORCID 0000-0001-9038-6688
Gaurav ChopraDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.ORCID 0000-0003-0942-7898
Purdue University West Lafayette · USCleveland Clinic Lerner College of Medicine · USCleveland Clinic · US

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
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
NCATS NIH HHS UL1 TR002529NCI NIH HHS P30 CA023168NIAAA NIH HHS P50 AA024333NIMH NIH HHS RF1 MH128866NINDS NIH HHS R01 NS112526
6 · The paper itself

Abstract

Several microglia-expressed genes have emerged as top risk variants for Alzheimer's disease (AD). Impaired microglial phagocytosis is one of the main proposed outcomes by which these AD-risk genes may contribute to neurodegeneration, but the mechanisms translating genetic association to cellular dysfunction remain unknown. Here we show that microglia form lipid droplets (LDs) upon exposure to amyloid-beta (Aβ), and that their LD load increases with proximity to amyloid plaques in brains from human patients and the AD mouse model 5xFAD. LD formation is dependent on age and disease progression and is prominent in the hippocampus in mice and humans. Despite differences in microglial LD load between brain regions and sexes in mice, LD-laden microglia exhibited a deficit in Aβ phagocytosis. Unbiased lipidomic analysis identified a decrease in free fatty acids (FFAs) and a parallel increase in triacylglycerols (TGs) as the key metabolic transition underlying LD formation. DGAT2, a key enzyme for converting FFAs to TGs, promotes microglial LD formation and is increased in 5xFAD and human AD brains. Inhibition or degradation of DGAT2 improved microglial uptake of Aβ and drastically reduced plaque load in 5xFAD mice, respectively. These findings identify a new lipid-mediated mechanism underlying microglial dysfunction that could become a novel therapeutic target for AD.

Indexed as

Alzheimer’s diseaseglialipid dropletslipidomicslipidsmetabolismMicroglianeurodegenerationphagocytosis

Identifiers

PMID37333071
PMCPMC10274698
OpenAlexW4379518790

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.