Background:Aducanumab(Adu),which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid,has been reported to reduce amyloid pathology and improve impaired cognition after administra...
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Background:Aducanumab(Adu),which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid,has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose(10 mg/kg)of the drug in Alzheimer’s disease(AD)clinical *** purpose of this study was to investigate the effects of a lower dose of Adu(3 mg/kg)with enhanced delivery via focused ultrasound(FUS)in an AD mouse ***:The FUS with microbubbles opened the blood-brain barrier(BBB)of the hippocampus for the delivery of *** combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly.Y-maze test,Brdu labeling,and immunohistochemical experimental methods were employed in this *** addition,RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental ***:The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the *** combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS *** treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD ***,RNA sequencing identified that 4 enriched canonical pathways including phagosome formation,neuroinflammation signaling,CREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined ***:In conclusion,the enhanced delivery of a low dose of Adu(3 mg/kg)via FUS decreases amyloid deposits and attenuates cognitive function ***-mediated BBB opening increases adult hippocampal neurogenesis as well as drug *** present an AD treatment strategy through the synergistic effect of the combined therapy of
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