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Updated: Jun 11, 2026
Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
A Polarity-Sensitive Lipid Droplet Probe Reveals Aβ Species-Dependent Lipid Droplet Remodeling in Microglia
Panyi Hu1,2, Shuo Guo3, Youxiang Ren4
1Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu610041, Sichuan, China.
Abstract:
Microglial lipid metabolic alterations are increasingly implicated in Alzheimer's disease (AD), yet the specific β-amyloid (Aβ) species involved in lipid droplet (LD) remodeling remain unclear. Precise visualization of LD morphology in complex biological systems is limited by the availability of selective and photostable probes. Herein, we report a polarity-sensitive LD probe, BODIPY-LD, constructed with a donor-π-acceptor-π-donor (D-π-A-π-D) framework that enables hydrophobic targeting and intramolecular charge transfer (ICT)-based fluorescence activation in low-polarity environments. The probe allows high-contrast visualization and quantitative assessment of LD morphology in cells and brain tissues. Using BODIPY-LD, we observed increased LD burden in hippocampal microglia of APP/PS1 mice and systematically compared the effects of different Aβ25-35 assembly states on LD accumulation in BV2 microglia. Among monomeric, oligomeric, and fibrillar Aβ25-35 forms, the monomer-treated BV2 cells showed the most pronounced LD enrichment under our experimental conditions. This LD-rich phenotype was associated with reduced phagocytic capacity and was partially reversible upon inhibition of LD synthesis using the long-chain acyl-CoA synthetases (ACSL) inhibitor Triacsin C. Together, these findings suggest that monomeric Aβ25-35 is associated with an LD-rich microglial phenotype and impaired phagocytic function in vitro model. Beyond this biological observation, BODIPY-LD provides a useful tool for studying lipid remodeling in neuroinflammatory contexts.
Insights
Researchers developed BODIPY-LD, a novel probe for visualizing lipid droplets (LDs). Monomeric beta-amyloid (Aβ) triggers an LD-rich microglial phenotype, impairing their function in Alzheimer's disease models.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Microglial lipid metabolism is crucial in Alzheimer's disease (AD).
- Specific beta-amyloid (Aβ) species driving lipid droplet (LD) remodeling are unknown.
- Existing probes lack selectivity and photostability for LD visualization.
Purpose of the Study:
- To develop a novel, selective, and photostable probe for visualizing LD morphology.
- To investigate the impact of different Aβ species on microglial LD accumulation.
- To explore the functional consequences of Aβ-induced LD remodeling in microglia.
Main Methods:
- Synthesis of a polarity-sensitive LD probe, BODIPY-LD, utilizing a D-π-A-π-D framework.
- High-contrast visualization and quantitative assessment of LDs in microglial cells and brain tissues.
- Comparative analysis of monomeric, oligomeric, and fibrillar Aβ₂₅₋₃₅ effects on LDs in BV2 microglia.
Main Results:
- BODIPY-LD enabled high-contrast visualization of LD morphology.
- APP/PS1 mouse hippocampus showed increased microglial LD burden.
- Monomeric Aβ₂₅₋₃₅ induced the most significant LD accumulation in BV2 microglia.
- LD-rich microglia exhibited reduced phagocytic capacity, partially reversible with ACSL inhibition.
Conclusions:
- Monomeric Aβ₂₅₋₃₅ is linked to an LD-rich microglial phenotype and impaired phagocytosis in vitro.
- BODIPY-LD is a valuable tool for studying lipid remodeling in neuroinflammation and AD.
- Targeting microglial lipid metabolism may offer therapeutic strategies for AD.
