Abstract
The glymphatic system is a “pseudo-lymphatic” perivascular network distributed throughout the brain, responsible for replenishing as well as cleansing the brain. Glymphatic clearance is the macroscopic process of convective fluid transport in which harmful interstitial metabolic waste products are removed from the brain intima. This paper addresses the glymphatic system, its dysfunction and the major consequences of impaired clearance in order to link neurodegeneration and glymphatic activity with lifestyle choices. Glymphatic clearance can be manipulated by sleep deprivation, cisterna magna puncture, acetazolamide or genetic deletion of AQP4 channels, but how lifestyle choices affect this brain-wide clearance system remains to be resolved. This paper will synthesize existing literature on glymphatic clearance, sleep, Alzheimer’s disease and lifestyle choices, in order to harness the power of this mass transport system, promote healthy brain ageing and possibly prevent neurodegenerative processes. This paper concludes that 1. glymphatic clearance plays a major role in Alzheimer’s pathology; 2. the vast majority of waste clearance occurs during sleep; 3. dementias are associated with sleep disruption, alongside an age-related decline in AQP4 polarization; and 4. lifestyle choices such as sleep position, alcohol intake, exercise, omega-3 consumption, intermittent fasting and chronic stress all modulate glymphatic clearance. Lifestyle choices could therefore alter Alzheimer’s disease risk through improved glymphatic clearance, and could be used as a preventative lifestyle intervention for both healthy brain ageing and Alzheimer’s disease.
Highlights
Discovered in 2012, the glymphatic system, which stands for glial-dependent lymphatic transport, has been categorized as a macroscopic waste clearance system
The brain consists of four aqueous compartments: cerebrospinal fluid (CSF), interstitial fluid (ISF), intracellular fluid and blood, all separated by two main barriers regulating their ionic and biochemical composition: the blood–brain barrier and the blood–CSF barrier [2]
Tight junctions on endothelial cells block the movement of macromolecules but allow fluids and solutes to diffuse into the brain from the perivascular space between endothelial cells and astrocytic endfeet [2]
Summary
Discovered in 2012, the glymphatic system, which stands for glial-dependent lymphatic transport, has been categorized as a macroscopic waste clearance system. This suggests the involvement of a mass transport system [3] This glial cell-dependent paravascular network removes soluble proteins and metabolites from the central nervous system, but in addition supplies the brain with glucose, lipids and neuromodulators, utilizing paravascular tunnels formed by astroglial cells [1,2,4]. Since this is a relatively new discovery, the amount of scientific literature surrounding the glymphatic system is rapidly increasing, and its definition is continuously being renewed. The movement of ISF along paravascular spaces of veins remains disputed, and some claim that a distinct route exists for
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