How strong is the evidence for sleep dependent glymphatic clearance in regards to Alzheimer's?
Year: 2026
Type: preprint
Abstract: Alzheimer's disease is mainly caused by two characteristic hallmarks: intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau proteins; and extracellular senile plaques due to the aggregation of Amyloid-β monomers. The cerebrospinal fluid is transported to the brain parenchyma, facilitated by AQP4 water channels on the endfeet of astrocytes, where it mixes with the interstitial fluid and leaves through the perivenous space. During delta wave sleep, the volume of interstitial spaces increases, and the cerebrospinal fluid flows more easily into the parenchyma, shown in rodent models. The production of Amyloid-β is also reduced. Over 60 studies were synthesised, and 40 studies were used. 6 studies were analysed based on their contribution to the effect of sleep on Alzheimer's, through the perspective of the glymphatic system, and their focus on tracers, injections and imaging as they can hamper results significantly. An analysis of the debate regarding convective bulk flow versus passive parenchymal diffusion and the effect of long sleep duration and the role of AQP4 is carried out, and the problems surrounding rodent models usage. Future research should focus on non-invasive tracers and, non-invasive high-resolution imaging in humans, and focus on the glymphatic system should be shifted from rodents to humans.
Author: Tasnim Rayna, Myshara
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225658406
Cites:
Cited by:
Related to: