REVIEW ARTICLE
GLYMPHATIC SYSTEM DISORDERS IN ALZHEIMER’S DISEASE
1
Student Scientific Association of Neurology, Wroclaw Medical University, Poland
2
Department of Neurology, University Centre of Neurology and Neurosurgery, Wroclaw Medical University, Poland
Submission date: 2025-12-13
Final revision date: 2026-01-17
Acceptance date: 2026-01-18
Online publication date: 2026-06-17
Corresponding author
Marta Koźmińczuk
Student Scientific Association of Neurology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland
Student Scientific Association of Neurology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Dysfunction of the glymphatic system (GS) impairs the removal of metabolites from the central nervous system, promoting neurotoxic change and the progression of Alzheimer’s disease (AD). AD is characterised by the abnormal accumulation of neurotoxic amyloid-b (Ab) and tau proteins within the brain.
Aim:
In this review, we aim to summarize current knowledge on GS dysregulation and its association with AD development and progression.
Material and methods:
A literature search was carried out using five scientific databases to identify English-language studies on GS alterations in AD in humans published within the last five years. After screening and eligibility assessment, 44 articles were included.
Results:
According to our research AD appears to be associated with GS impairment. The most frequently reported indicators of GS dysfunction were the analysis along the perivascular space (ALPS) index, choroid plexus (CP) enlargement, and enlarged perivascular spaces (EPVS). A low ALPS-index is used as an indicator of GS dysfunction. Patients with AD show significantly reduced ALPS-index and an increased number of EPVS than controls. CP plays a crucial role in Ab clearance, and CP enlargement is considered a manifestation of its dysfunction, as observed in patients with AD. GS dysfunction may also be indicated by genetic factors and physiological modulations.
Conclusions:
The review demonstrated that dysfunction of the GS disrupts the drainage of cerebrospinal and interstitial fluid, leading to impaired removal of metabolites, accumulation of Ab, and progressive neurodegeneration in AD.
Dysfunction of the glymphatic system (GS) impairs the removal of metabolites from the central nervous system, promoting neurotoxic change and the progression of Alzheimer’s disease (AD). AD is characterised by the abnormal accumulation of neurotoxic amyloid-b (Ab) and tau proteins within the brain.
Aim:
In this review, we aim to summarize current knowledge on GS dysregulation and its association with AD development and progression.
Material and methods:
A literature search was carried out using five scientific databases to identify English-language studies on GS alterations in AD in humans published within the last five years. After screening and eligibility assessment, 44 articles were included.
Results:
According to our research AD appears to be associated with GS impairment. The most frequently reported indicators of GS dysfunction were the analysis along the perivascular space (ALPS) index, choroid plexus (CP) enlargement, and enlarged perivascular spaces (EPVS). A low ALPS-index is used as an indicator of GS dysfunction. Patients with AD show significantly reduced ALPS-index and an increased number of EPVS than controls. CP plays a crucial role in Ab clearance, and CP enlargement is considered a manifestation of its dysfunction, as observed in patients with AD. GS dysfunction may also be indicated by genetic factors and physiological modulations.
Conclusions:
The review demonstrated that dysfunction of the GS disrupts the drainage of cerebrospinal and interstitial fluid, leading to impaired removal of metabolites, accumulation of Ab, and progressive neurodegeneration in AD.
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