Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer's disease: an updated overview of nonpharmacological therapies.

Douglas A Formolo, Jiasui Yu, Kangguang Lin, Hector W H Tsang, Haining Ou, Georg S Kranz, Suk-Yu Yau

Journal: Molecular neurodegeneration 2023;18(1):26

PMID: 37081555

Free Full Text on BioMed Central View on PubMed

Abstract

["Understanding and treating Alzheimer's disease (AD) has been a remarkable challenge for both scientists and physicians. Although the amyloid-beta and tau protein hypothesis have largely explained the key pathological features of the disease, the mechanisms by which such proteins accumulate and lead to disease progression are still unknown. Such lack of understanding disrupts the development of disease-modifying interventions, leaving a therapeutic gap that remains unsolved. Nonetheless, the recent discoveries of the glymphatic pathway and the meningeal lymphatic system as key components driving central solute clearance revealed another mechanism underlying AD pathogenesis. In this regard, this narrative review integrates the glymphatic and meningeal lymphatic systems as essential components involved in AD pathogenesis. Moreover, it discusses the emerging evidence suggesting that nutritional supplementation, non-invasive brain stimulation, and traditional Chinese medicine can improve the pathophysiology of the disease by increasing glymphatic and\/or meningeal lymphatic function. Given that physical exercise is a well-regarded preventive and pro-cognitive intervention for dementia, we summarize the evidence suggesting the glymphatic system as a mediating mechanism of the physical exercise therapeutic effects in AD. Targeting these central solute clearance systems holds the promise of more effective treatment strategies.",{"copyright":"\u00a9 2023. The Author(s)."}]

Address: Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hung Hom, Kowloon, Hong Kong, S.A.R, China.; Research Institute for Smart Ageing (RISA), The Hong Kong Polytechnic University, Hong Kong S.A.R, China.; Mental Health Research Center (MHRC), The Hong Kong Polytechnic University, Hong Kong S.A.R, China.; Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.; School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao City, Shandong Province, China.; Department of Rehabilitation, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.; Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria.; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong S.A.R, China.; Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, 11 Yuk Choi Road, Hung Hom, Kowloon, Hong Kong, S.A.R, China. [email protected].; Research Institute for Smart Ageing (RISA), The Hong Kong Polytechnic University, Hong Kong S.A.R, China. [email protected].; Mental Health Research Center (MHRC), The Hong Kong Polytechnic University, Hong Kong S.A.R, China. [email protected].

DOI: 10.1186/s13024-023-00618-3

Link outs

Free resources

Full Text Sources:

Medical:

Miscellaneous:

https://assays.cancer.gov/CPTAC-1548

MeSH Terms: Humans, Alzheimer Disease, Brain, Lymphatic System, Glymphatic System, Amyloid beta-Peptides