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The glymphatic system in neurodegenerative diseases and brain tumors: mechanistic insights, biomarker advances, and therapeutic opportunities
The brain’s waste clearance system in neurodegenerative diseases and brain tumors: how it works, new markers, and treatment possibilities
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Abstract
Glymphatic dysfunction is associated with neurodegenerative diseases and brain tumors, leading to impaired waste clearance and immune modulation.
- Impaired glymphatic function can lead to the accumulation of neurotoxic proteins such as amyloid-β, tau, and α-synuclein in Alzheimer's and Parkinson's diseases.
- Factors contributing to glymphatic dysfunction include loss of polarization, reduced arterial pulsatility, genetic risks, and sleep disturbances.
- Neuroimaging biomarkers like the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus volume (CPV) can quantify glymphatic function and correlate with clinical decline.
- In brain tumors, mechanical compression and lactate-driven acidosis obstruct perivascular fluid transport, leading to a reduced ALPS index that correlates with tumor grade and survival.
- Emerging therapies aimed at restoring function include pharmacological interventions, non-invasive techniques, and surgical approaches.
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Key numbers
40–60%
Reduction in CSF–ISF exchange efficiency in AD
Efficiency of CSF–ISF exchange is reduced due to dysfunction.
30%
Decrease in glymphatic clearance efficiency in PD
Efficiency is reduced due to obstruction by α-synuclein aggregates.
30–50%
Increase in glymphatic clearance efficiency from pharmacological modulation
Pharmacological interventions can enhance glymphatic clearance.