The role of the glymphatic (brain) system in the pathogenesis of Alzheimer disease: a systematic literature review
Year: 2026
Type: review
Study design: Systematic Review
Abstract: Introduction: Alzheimer's disease (AD) is the most common form of dementia, characterized by memory impairment, perceptual disturbances, and cognitive-executive dysfunctions, associated with the deposition of amyloid plaques and neurofibrillary tangles.Recent evidence highlights the role of the glymphatic system in the clearance of toxic products from the brain parenchyma through cerebrospinal fluid (CSF) circulation.AQP4 which is selectively localized at the astrocytic endfeet, serves as a critical mediator, regulating CSF transport.Alterations in its expression or polarity leads to impaired clearance and subsequent accumulation of β-amyloid and protein tau.Sleep enhances CSF flow and metabolite removal, whereas sleep deprivation and poor sleep quality restricts it.Finally, aging -the primary risk factor for the AD development-is accompanied by vascular and cellular structural changes and a decline in glymphatic efficiency.Aim: The present systematic review aims to investigate the role of the glymphatic system in the pathogenesis of AD, with particular emphasis on the mechanisms related to: (a) the expression and functionality of AQP4, (b) the effect of sleep on glymphatic system function, and (c) the changes associated with aging.Methodology: A systematic review of international studies was conducted via PUBMED database.The final search strategy was: ("glymphatic system"[Title/Abstract] AND "alzheimer*"[Title/Abstract]) AND (english [Filter]).The cutoff date was set at 11/11/2024.Additionally, a secondary search was performed in the reference lists of the selected articles retrieved from the database. Results:The database search yielded 432 records, of which only 59 were included in the review.The secondary search in the reference lists of the selected articles yielded the additional number of 59 records.The role of the glymphatic system in AD pathogenesis was examined, specifically focusing on the mechanisms through which various regulatory factors influence the functionality and effectiveness of the glymphatic system in clearing toxic agents within the parenchyma. Conclusions: Alterations in AQP4 expression and polarity, sleep disturbances, and age-relatedchanges are critical regulators of glymphatic activity, contributing to the pathogenesis of AD.
Author: Κέδρας, Θωμάς Ν.
Language: Greek
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7159742123