RESUMEN
Drainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic-lymphatic clearance lead to the accumulation beta-amyloid (Aß) in dementia models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved Aß drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute Aß clearance from brain, but not plaques, to cerebrospinal fluid (CSF) space and then deep cervical lymph node (dCLN). dCLN ligation exaggerated memory impairment and progress of plaque formation and also the beneficial effects of FUS-MB upon Aß removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of Aß in CSF. In conclusion, FUS-MB enhances glymphatic-lymphatic clearance of Aß mainly by increasing brain-to-CSF Aß drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of Aß disposal through CSF-lymphatics.