2. Academic Validation
  3. Cranial bone maneuver ameliorates Alzheimer's disease pathology via enhancing meningeal lymphatic drainage function

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

  • Alzheimers Dement. 2025 Feb;21(2):e14518. doi: 10.1002/alz.14518.
Xuan Lu 1 2 3,  Shanshan Bai 1 2 3,  Lu Feng 3,  Xu Yan 1 2,  Yuejun Lin 1 2 4,  Junzhe Huang 5,  Xulin Liao 6,  Haixing Wang 1 2 3 4,  Linlong Li 3,  Zhengmeng Yang 3,  Leo Yik Chun Yan 5,  Boguang Yang 1 2 7,  Ming Wang 1 2,  Jiakang Jin 1 2,  Zhixian Zong 1 2,  Zhaowei Jiang 1 2,  Chuiguo Huang 8,  Chaoran Liu 2,  Xiaoting Zhang 1 2,  Han Su 1 2 9,  Yaofeng Wang 3,  Wayne Yuk-Wai Lee 1 2,  Xiaohua Jiang 10,  Micky D Tortorella 3,  Sien Lin 1 2,  Ho Ko 5,  Gang Li 1 2 4
Affiliations

Affiliations

  • 1 Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China.
  • 2 Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, PR China.
  • 3 Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, PR China.
  • 4 Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
  • 5 Division of Neurology, Department of Medicine and Therapeutics & Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • 6 Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • 7 Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • 8 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
  • 9 Department of Neurosurgery, First Hospital of Jilin University, Changchun, PR China.
  • 10 MOE Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
PMID: 39887820 DOI: 10.1002/alz.14518
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.

Keywords

Alzheimer's disease; Interleukin 6; cranial bone maneuver; lymphangiogenesis; meningeal lymphatic vessels; vascular endothelial growth factor C.

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