Objective:

To critically examine the methodologies for evaluating glymphatic function in humans and the evidence supporting the existence of the glymphatic system, particularly in relation to CNS diseases.

Key Findings:

• The glymphatic system is crucial for clearing waste from the brain and is most active during sleep, with significant implications for CNS diseases.
• Impaired glymphatic function is associated with the accumulation of toxic waste, including amyloid-β, tau, and α-synuclein, and may play a role in dementia diseases.
• Current human methodologies for assessing glymphatic function include intrathecal contrast-enhanced MRI, intravenous contrast-enhanced MRI, DTI-ALPS, assessment of perivascular spaces, and magnetic resonance encephalography, each with its own limitations.

Interpretation:

While the glymphatic system shows promise in understanding CNS diseases, the majority of research is animal-based, and human translation remains uncertain, highlighting the need for further studies.

Limitations:

• Most research on the glymphatic system has been conducted in animals, raising questions about human applicability and potential biases in methodologies.
• Current imaging methods have significant limitations and may not accurately reflect glymphatic function, necessitating the development of more reliable techniques.

Conclusion:

Further research is needed to validate the glymphatic system's role in human health and disease, alongside the urgent development of reliable assessment methods.