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Abstract
Drainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic–lymphatic clearance lead to the accumulation beta-amyloid (Aβ) in dementia models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved Aβ drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute Aβ 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 Aβ removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of Aβ in CSF. In conclusion, FUS-MB enhances glymphatic–lymphatic clearance of Aβ mainly by increasing brain-to-CSF Aβ drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of Aβ disposal through CSF-lymphatics.
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1 Seoul National University, Department of Nuclear Medicine, College of Medicine, Seoul, South Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul, South Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
2 Seoul National University, Department of Nuclear Medicine, College of Medicine, Seoul, South Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905)
3 Seoul National University Hospital, Biomedical Research Institute, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X); Seoul National University Hospital, Department of Radiology, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X)
4 Seoul National University Hospital, Department of Radiology, Seoul, South Korea (GRID:grid.412484.f) (ISNI:0000 0001 0302 820X)