Brain waste clearance via the nose declines with age
The brain has its own drainage system for metabolic waste. It deteriorates with age, and that deterioration is linked to the protein build-up seen in dementia. A new study has mapped a key part of that drainage route in remarkable detail.
Between the olfactory bulbs at the front of the brain and the perforated bone separating the brain from the nasal cavity, researchers identified a specialised lymphatic network. The researchers found numerous microscopic openings in the arachnoid membrane, a layer of the meninges (the membranes covering the brain), measuring approximately 2 to 12 micrometres in diameter. Through these openings, cerebrospinal fluid flows directly into meningeal lymphatic vessels, and from there into lymph nodes in the neck.
A route that fails with age
When the openings were physically blocked with microspheres, drainage of cerebrospinal fluid to cervical lymph nodes dropped dramatically, confirming their functional importance. Similar structures were also identified in cynomolgus monkeys, suggesting the system is evolutionarily conserved beyond mice.
In aged mice, the openings were smaller and the lymphatic vessels less active. The researchers then treated older mice intranasally with VEGF-C, a signalling molecule that promotes lymphatic vessel growth. This less invasive nasal route selectively expanded lymphatic vessels around the olfactory bulbs, partially improving drainage. Full restoration of the age-related decline was not achieved, but the findings are relevant for dementia research: Alzheimer’s disease originates in precisely the brain region that sits on this drainage route.
A less invasive approach
Earlier strategies for improving cerebrospinal fluid flow required penetrating the meninges. The nasal delivery tested here is less invasive. This is animal research; whether the approach works safely in humans remains to be established. But the detailed mapping of an ageable and partially restorable brain-waste clearance route provides a meaningful target for future therapeutic development.
Search terms to explore further: glymphatic system cerebrospinal fluid, meningeal lymphatic vessels aging, VEGF-C neural lymphangiogenesis