Cranial bone maneuver ameliorates Alzheimer's disease pathology via enhancing meningeal lymphatic drainage function

Abstract

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Recent research highlights meningeal lymphatics as key regulators in neurological diseases, suggesting that enhancing their drainage function could be a potential therapeutic strategy for AD. Our proof-of-concept study demonstrated that cranial bone transport can improve meningeal lymphatic drainage function and promote ischemic stroke recovery. METHODS: This study defined cranial bone maneuver (CBM) technique. After osteotomy, a small circular bone flap was made and attached to an external fixator for subsequent maneuver in a controlled fashion for a defined period using 5xFAD mice. RESULTS: CBM treatment improved memory functions, reduced amyloid deposits, and promoted meningeal lymphatic drainage function. CBM induced cascades of inflammatory and lymphangiogenic processes in skull and meninges. Meningeal lymphatics are indispensable elements for the therapeutic effects of CBM. DISCUSSION: CBM might be a promising innovative therapy for AD management, warranting further clinical investigation. Highlights: Cranial bone maneuver (CBM) alleviated memory deficits and amyloid depositions. CBM promoted meningeal lymphangiogenesis and lymphatic drainage function. The beneficial effects of CBM lasted for a long time following the CBM procedures. CBM induced cascades of inflammatory and lymphangiogenic processes in the meninges. Meningeal lymphatic vessels are indispensable elements for CBM therapeutic effects.