Targeting microglia with mannose-coated nanoparticles to improve pathology and behavior in a mouse model of Alzheimer’s disease.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B546
Abstract ID: 5378

Presenting Author:
Asmaa A badr , Post-doctoral researcher at Ohio State Univ. Col. of Med.

Abstract:

Neuroinflammation is a hallmark of Alzheimer’s disease (AD) pathobiology. Microglia in AD brains show elevated levels of microRNA-17 (miR-17), which maintains a balance between pro- and anti-inflammatory cytokine production. Microglia play an essential role in the production of cytokines; however, the role of microglial miR-17 in controlling neuroinflammation is not clear. We hypothesized that targeting miR-17 in microglia in vivo will decrease neuroinflammation and dampen immune cell activation, reducing amyloid beta (Aβ) deposition and preventing behavioral changes in AD mice. We generated mannose-coated lipid nanoparticles (MLNPs) enclosing an inhibitor to miR-17 (Anti-17 MLNPs) as mannose binds receptors on microglia. We used a 5XFAD mouse model that recapitulates AD-related phenotypes observed in humans. Anti-17 MLNPs were delivered to 5XFAD mouse brains by intra-cisterna magna injection. Our results show that MLNPs specifically deliver Anti-17 to microglia in vivo and in vitro. Anti-17 MLNPs attenuated the microglial inflammatory response to Aβ. Also, the Aβ burden in the brains of Anti-17 MLNPs mice was significantly lowered. A significant decrease in immune cell activation and cytokine production pathways was also identified in the brains of Anti-17 MLNPs-injected mice. This reduced spatial memory deterioration and decreased anxiety-like behavior in 5XFAD mice. We concluded that specific targeting of microglia with miR-17 antagomir improves pathology in AD.