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Review
. 2024 Jun 29;16(6):e63448.
doi: 10.7759/cureus.63448. eCollection 2024 Jun.

Role of the Glymphatic System in Alzheimer's Disease and Treatment Approaches: A Narrative Review

Mansi Thipani Madhu  1 , Ojas Balaji  2 , Venkataramana Kandi  3 , Jayashankar Ca  1 , Ganaraja V Harikrishna  4 , Nirosha Metta  5 , Vamsi Krishna Mudamanchu  5 , Bhangdiya G Sanjay  1 , Praful Bhupathiraju  1
Affiliations
Review

Role of the Glymphatic System in Alzheimer's Disease and Treatment Approaches: A Narrative Review

Mansi Thipani Madhu et al. Cureus. .

Abstract

Currently, there is unavailability of disease-modifying medication for Alzheimer's disease (AD), a debilitating neurological disorder. The pathogenesis of AD appears to be complex and could be influenced by the glymphatic system present in the central nervous system (CNS). Amyloid-beta (Aβ) and other metabolic wastes are eliminated from the brain interstitium by the glymphatic system, which encompasses perivascular channels and astroglial cells. Dysfunction of the glymphatic system, which could occur due to decreased aquaporin 4 (AQP4) expression, aging-related alterations in the human brain, and sleep disruptions, may contribute to the pathogenesis of AD and also accelerate the development of AD by causing a buildup of harmful proteins like Aβ. Promising approaches have been examined for reducing AD pathology, including non-pharmacological therapies that target glymphatic function, like exercise and sleep regulation. In addition, preclinical research has also demonstrated the therapeutic potential of pharmaceutical approaches targeted at augmenting AQP4-mediated glymphatic flow. To identify the precise processes driving glymphatic dysfunction in AD and to find new treatment targets, more research is required. Innovative diagnostic and treatment approaches for AD could be made possible by techniques such as dynamic contrast-enhanced MRI, which promises to evaluate glymphatic function in neurodegenerative diseases. Treatment options for AD and other neurodegenerative diseases may be improved by comprehending and utilizing the glymphatic system's function in preserving brain homeostasis and targeting the mechanisms involved in glymphatic functioning. This review intends to enhance the understanding of the complex link between AD and the glymphatic system and focuses on the function of AQP4 channels in promoting waste clearance and fluid exchange.

Keywords: alzheimer’s disease; aqp4; aquaporins; brain health; glymphatic system; lymphatic system; neurogenerative diseases; physical exercise; sleep.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Role of the glymphatic system in preventing neurodegenerative diseases like Alzheimer's disease
Image created by author Venkataramana Kandi
Figure 2
Figure 2. Pathogenesis, prevention, and management of Alzheimer's disease
Image created by author Venkataramana Kandi
See this image and copyright information in PMC

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