Hybrid Lipoplex Boosts Neuron‐Microglia Crosstalk for Treatment of Alzheimer's Disease through A β ‐Targeted‐Autophagy and ApoE2 Gene Supplementation

benefit pApoE2 transfection in neurons, enabling the transport of Aβ into microglia, and facilitating enzymatic hydrolysis and cellular digestion of extracellular Aβ. The lipoplex-boosted neuron-microglia interactions ultimately eliminate both intra- and extra-cellular Aβ aggregates. Consequently, the RMC/pApoE2 lipoplex eliminates ≈86.9% of Aβ plaques in the hippocampus of APP/PS1 mice and restored the synaptic function and neuronal connectivity. Moreover, it recovers the spatial memory of APP/PS1 mice to nearly the level of WT control. The presented hybrid lipoplex showcases an advanced gene delivery system, and offers a promising strategy for Aβ clearance in AD treatment.