The brain lacks conventional lymphatic drainage, relying instead on intricate fluid transport systems to eliminate toxins, distribute nutrients, and regulate immune surveillance. The glymphatic system, in particular, facilitates the exchange of CSF and interstitial fluid (ISF) along perivascular pathways, operating predominantly during sleep. Alongside meningeal lymphatics and cerebrovascular networks, this clearance axis is crucial for maintaining the delicate balance of the brain’s internal environment. With advancing age, these systems exhibit structural and functional decline, coinciding with the accumulation of pathological proteins such as amyloid-β and tau. Disruption of neurofluid dynamics is now recognized not only in classical neurodegenerative disorders but also in cerebrovascular disease, traumatic brain injury, and even psychiatric conditions. Emerging technologies ranging from advanced neuroimaging and computational modeling to novel biomarkers and interventional strategies offer opportunities to investigate and modulate these pathways.

The central nervous system relies on specialized fluid dynamics systems such as the glymphatic pathway, cerebrospinal fluid (CSF) flow, and meningeal lymphatics to remove metabolic waste and maintain neural homeostasis. Growing evidence indicates that dysfunction in these clearance systems contributes significantly to the onset and progression of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and other age-related cognitive disorders. Despite recent advances, key questions remain regarding how these systems are altered across the lifespan, how their impairment influences disease mechanisms, and how they can be targeted therapeutically. This Research Topic aims to bring together interdisciplinary contributions that explore neurofluid dynamics and brain clearance pathways across the spectrum of aging and disease.

This Research Topic welcomes original research, reviews, mini-reviews, methods papers, and perspectives that explore the role of neurofluid dynamics and brain clearance pathways in aging and neurological disease. We invite contributions across molecular, cellular, systems, and translational neuroscience that address:

- Mechanisms of glymphatic, CSF, and meningeal lymphatic function and dysfunction
- Age-related alterations in brain fluid clearance and their link to neurodegeneration
- Neuroimaging, fluid biomarkers, and computational modeling of clearance pathways
- Interactions between vascular, lymphatic, and glymphatic systems
- Sleep, circadian rhythm, and lifestyle factors affecting fluid homeostasis
- Therapeutic strategies to enhance clearance, including pharmacological and non-pharmacological interventions

Interdisciplinary and translational studies are particularly encouraged.

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Neurofluid dynamics and brain clearance pathways in aging and disease: From mechanisms to therapy