Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer's disease model

Drainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic-lymphatic clearance lead to the accumulation beta-amyloid (A{beta}) in dementia models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved A{beta} drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute A{beta} 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 A{beta} removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of A{beta} in CSF. In conclusion, FUS-MB enhances glymphatic-lymphatic clearance of A{beta} mainly by increasing brain-to-CSF A{beta} drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of A{beta} disposal through CSF-lymphatics.