Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (doi:10.21979/N9/V4FHSQ)

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Document Description

Citation

Title:

Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model

Identification Number:

doi:10.21979/N9/V4FHSQ

Distributor:

DR-NTU (Data)

Date of Distribution:

2024-09-30

Version:

1

Bibliographic Citation:

Ruedl, Christiane; Wu, Xiaoting, 2024, "Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model", https://doi.org/10.21979/N9/V4FHSQ, DR-NTU (Data), V1

Study Description

Citation

Title:

Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model

Identification Number:

doi:10.21979/N9/V4FHSQ

Authoring Entity:

Ruedl, Christiane (Nanyang Technological University)

Wu, Xiaoting (Nanyang Technological University)

Software used in Production:

Flowjo

Grant Number:

Tier2 grant (MOE-T2EP30121-0004)

Distributor:

DR-NTU (Data)

Access Authority:

Ruedl, Christiane

Depositor:

Ruedl, Christiane

Date of Deposit:

2024-04-22

Holdings Information:

https://doi.org/10.21979/N9/V4FHSQ

Study Scope

Keywords:

"Medicine, Health and Life Sciences", Microglia, Alzheimer’s disease, Lipid droplets, Phagocytosis

Abstract:

Macrophages accumulate lipid droplets (LD) under stress and inflammatory conditions. Despite the presence of LD-loaded macrophages in many tissues, including the brain, their contribution to neurodegenerative disorders remains elusive. This study investigated the role of lipid metabolism in Alzheimer’s disease (AD) by assessing the contribution of LD-loaded brain macrophages, including microglia and border-associated macrophages (BAMs), in an AD mouse model. In particular, activated CD11c+ microglia, localized proximal to beta-amyloid (Aβ) plaques, had a pronounced lipid-associated gene signature and a higher LD load than other microglial subtypes. Having observed that elevated intracellular LD content correlated inversely with microglial phagocytic activities, we subsequently inhibited LD formation specifically in CX3CR1+ brain macrophages using an inducible transgenic mouse model. Reducing the lipid load of microglia and CX3CR1+ BAMs improved phagocytic and efferocytic capacities and significantly reduced Aβ deposition in the brain. Therefore, mitigating LD accumulation in microglia and BAMs provides new perspectives for the treatment of AD.

Kind of Data:

Flow cytometry raw data

Methodology and Processing

Sources Statement

Data Access

Other Study Description Materials

Related Publications

Citation

Identification Number:

10.1126/sciadv.adq6038

Bibliographic Citation:

Wu, X., Miller, J. A., Lee, B. T. K., Wang, Y., & Ruedl, C. (2025). Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model. Science Advances, 11(6), eadq6038.

Citation

Identification Number:

10356/184421

Bibliographic Citation:

Wu, X., Miller, J. A., Lee, B. T. K., Wang, Y. & Ruedl, C. (2025). Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer's disease mouse model. Science Advances, 11(6), eadq6038-.

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Supplementary Figure S9_2.7z

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Lipidomic analysis.csv

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