Cellular and molecular processes that are of key importance in the development of neuroinflammation and increased cytokine response, activation of microglia and astrogliosis, contributing to the accumulation of metabolites and aberrant proteins in the brain tissue due to their overproduction and insufficient clearance, concomitant disturbance of architecture and sleep patterns are interconnected and induce brain aging with the formation its complex neurobiological mechanism. The study of these processes brings us closer to understanding the main determinants of healthy and unhealthy aging, primary prevention and preclinical diagnosis of age-related diseases, as well as to solving problems of longevity and increasing quality of life. The imbalance of homeostatic functions that support the exchange of fluids and solutes in the brain tissue is observed both in physiological aging and in the development of pathology of the nervous system with long-term consequences - from impaired synaptic signaling to the development of neurodegenerative diseases. Dementia is one of the major health problems worldwide and is very complex in terms of pathophysiology. Therefore, one of the priorities of fundamental neurobiology is to elucidate the main morbid mechanisms of Alzheimer's disease as the most common form of dementia. The hypotheses of β-amyloid and tau protein largely explain the main pathological features of Alzheimer's disease, however, there remains a need for further research on biomarkers with high validity and predictive applicability in people without cognitive impairment and clinical symptoms and in the early stages of the disease. There is a need to intensify the search for effective solutions to slow or stop the progression of the disease, especially therapeutic approaches that modify the disease at the preclinical stage, when it is most beneficial to change its course. At the same time, the discovery of aquaporin-dependent clearance pathways in the brain made it possible to identify new mechanisms underlying the etiology and progression of neurodegeneration and neuroinflammation. Glial-mediated clearance plays a fundamental role in the process of physiological aging, the development of age-related changes in the brain, and neurodegenerative processes. We analyzed 273 articles posted in PubMed database selected by keywords "glymphatic system, Alzheimer's disease, dementia, amyloid Aβ, aquaporin, aging, brain clearance". A total of 102 full-text articles were included in this review. This article presents up-to-date evidence on the causes and consequences in the study of the relationship between dysfunction of the glymphatic pathway and the accumulation of pathological proteins with insufficient excretion of toxic metabolites from the brain parenchyma, which is considered a key factor in the development of Alzheimer's dementia.
Keywords: glymphatic - dementia - neurodegeneration - Alzheimer's disease - amyloid Aβ - aquaporin - aging - brain clearance.