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Abstract #118952 Published in IGR 24-4

AIBP controls TLR4 inflammarafts and mitochondrial dysfunction in a mouse model of Alzheimer's disease

Kim YS; Choi SH; Kim KY; Navia-Pelaez JM; Perkins GA; Choi S; Kim J; Nazarenkov N; Rissman RA; Ju WK; Ellisman MH; Miller YI
bioRxiv : the preprint server for biology 2024; 0:


Microglia-driven neuroinflammation plays an important role in the development of Alzheimer's disease (AD). Microglia activation is accompanied by the formation and chronic maintenance of TLR4 inflammarafts, defined as enlarged and cholesterol-rich lipid rafts serving as an assembly platform for TLR4 dimers and complexes of other inflammatory receptors. The secreted apoA-I binding protein (APOA1BP or AIBP) binds TLR4 and selectively targets cholesterol depletion machinery to TLR4 inflammaraft expressing inflammatory, but not homeostatic microglia. Here we demonstrated that amyloid-beta (Aβ) induced formation of TLR4 inflammarafts in microglia in vitro and in the brain of APP/PS1 mice. Mitochondria in APP/PS1 microglia were hyperbranched and cupped, which was accompanied by increased ROS and the dilated ER. The size and number of Aβ plaques and neuronal cell death were significantly increased, and the animal survival was decreased in APP/PS1 compared to APP/PS1 female mice. These results suggest that AIBP exerts control of TLR4 inflammarafts and mitochondrial dynamics in microglia and plays a protective role in AD associated oxidative stress and neurodegeneration.

Department of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.

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15 Miscellaneous



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