Background:  The glymphatic system (GS) has been described as a clearance and delivery system that utilizes perivascular spaces and convective flow to facilitate CSF and ISF exchange. Recent research has revealed a strong link between global glymphatic function and Alzheimer’s disease (AD) pathology. Emerging research suggests this system is crucial in effectively processing and clearing metabolites previously implicated in AD pathology. This literature review also explores how aging and lifestyle choices, such as dietary intake and sleep habits, alter the glymphatic function and may ultimately contribute to AD pathology.

Methods:  The articles reviewed included primary journal articles. The literature search was conducted using PubMed as a database, with key search terms such as “glymphatic system”, “Alzheimer’s disease”, and “sleep and glymphatic function”

Results: AQP4 channels play a key role in the GS, a recently discovered network that mediates the bulk flow of CSF-ISF across the brain parenchyma. The GS is impaired in several neurological disorders, including AD, and AQP4 channels have been implicated in the pathogenesis and progression of AD. Aging has been shown to cause AQP4 mislocalization, which impairs GS function and leads to the accumulation of amyloid-beta (Aβ) in the brain due to reduced waste clearance. The GS is more active during sleep, which allows for more efficient interstitial waste clearance (including soluble Aβ). Sleep deprivation has also been shown to GS activity, AQP4 depolarization and cause buildup of Aβ, increasing the AD risk. A recent study has identified the GS as important in clearing extracellular tau, preventing aggregation and neurodegeneration. AQP4 facilitates the transport of extracellular tau from the brain to the cerebrospinal fluid (CSF) and then to the deep cervical lymph nodes.

Conclusion: Aging and lifestyle factors can disrupt the GS, leading to neurodegeneration and cognitive decline. Sleeping regularly may help improve glymphatic function and reduce the risk of AD. The glymphatic system is a novel target for understanding and treating AD, but more research is needed to elucidate its mechanisms and interactions with other factors.

References and Resources

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