Glymphatic brain system and its role in pathogenesis of Alzheimer’s disease

Abstract

Alzheimer’s disease is the most common disease leading to the development of cognitive impairment and dementia. The pathological basis of the disease is the formation of amyloid plaques and neurofibrillary tangles. Also important are neuroinflammation, dysregulation of the blood-brain barrier, impaired clearance and accumulation of β-amyloid in the parenchyma and blood vessels of the brain, impaired synaptic transmission. Atherosclerosis, diabetes mellitus and the presence of epsilon-4 apolipoprotein E alleles are identified as one of the main risk factors in the pathogenesis of sporadic Alzheimer’s disease. It is assumed that the accumulation of β-amyloid is the result of an imbalance between its production and clearance. To develop an effective strategy for slowing down or stopping a neurodegenerative process, it is important to understand how β-amyloid is derived from the brain. The clearance of extracellular β-amyloid can occur through various systems, however, transport through the blood-brain barrier is of the greatest interest. recent studies have demonstrated the importance of the lymphatic system in removing β-amyloid from the brain through the perivascular spaces of Virkhov-Roben. Interestingly, the lymphatic system functions mainly during sleep and to a large extent reduces its activity during wakefulness. Since the concept of this system is relatively new, its the main structural elements are considered in the research, organization, regulation, and functions. Considering the variety of hypotheses that are considered as the basis of the pathogenesis of Alzheimer’s disease, we attempted to combine these data into a single unifying model and demonstrate the significance of the balance between synthesis and the ability of β-amyloid elimination from the brain.

Keywords

Alzheimer diseases / β-amyloid / perivascular Virkhov-Roben space / glymphatic system / sleep disorders / cognitive impairment / dementia / memory impairment / apolipoprotein E / Aβ-clearance / neurofibrillary tangle / amyloid plaques

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RIGHTS & PERMISSIONS

Lobzin V.Yu., Kolmakova K.A., Emelin A.Yu., Lapina A.V.