Korean researchers identify hidden brain waste-clearance pathway, offering clues to dementia treatment

The IBS Vascular Research Center team behind the study. From left: Director Ko Gou-young, Senior Researcher Hong Sun-pyo and Researcher Jin Cheol-hwa. [Ministry of Science and ICT]

South Korean researchers have identified, for the first time, a hidden drainage route through which cerebrospinal fluid clears waste from the brain — waste linked to degenerative conditions such as Alzheimer's disease. The team also proposed a new treatment strategy to restore the waste-clearing function that declines with age.

The Ministry of Science and ICT announced Wednesday that a research team led by Ko Gou-young, director of the Institute for Basic Science's Vascular Research Center, had used animal experiments to map the key pathway by which cerebrospinal fluid passes through the meninges — the membranes surrounding the brain — and is absorbed into meningeal lymphatic vessels for drainage.

The findings were published online Wednesday in Cell, one of the world's most prestigious scientific journals.

The brain continuously generates waste as a byproduct of its metabolic activity. That waste is carried out of the brain by cerebrospinal fluid, and this "brain-cleaning" process is essential to maintaining healthy brain function. When cerebrospinal fluid production and drainage are disrupted, neurotoxic proteins such as amyloid beta can accumulate in the brain, potentially leading to Alzheimer's and other degenerative neurological diseases.

In earlier studies published in Nature in 2019 and 2024, the team established that cerebrospinal fluid drains through meningeal lymphatic vessels at the base of the brain and through nasopharyngeal lymphatic networks into cervical lymph nodes, and that this pathway deteriorates with age. A 2025 study further identified a new drainage route through lymphatic vessels beneath the facial skin around the eyes and nose, and confirmed that gentle mechanical stimulation could promote drainage.

What had long remained unresolved, however, was how cerebrospinal fluid crosses the arachnoid mater — a tough, protective layer of the meninges — to reach the meningeal lymphatic vessels in the outer dural layer.

The team's latest research identified the gateway through which cerebrospinal fluid exits the arachnoid mater, naming it "arachnoid fenestrations" — microscopic pores in the membrane. The discovery completes the full picture of the drainage pathway: cerebrospinal fluid passes through these fenestrations, then travels through meningeal lymphatic vessels and nasal cavity lymphatics before reaching the cervical lymph nodes.

To visualize the microscopic drainage route, the researchers used specially engineered mice with fluorescently labeled lymphatic vessels alongside advanced three-dimensional imaging technology. The imaging clearly captured direct connections between lymphatic vessels in the olfactory bulb at the front of the brain and those in the nasal cavity, separated only by the cribriform plate — a thin bone between the brain and nasal cavity.

Scanning electron microscopy then directly confirmed the drainage pathway through which brain waste exits.

A schematic diagram showing the cerebrospinal fluid drainage pathway through arachnoid fenestrations into the olfactory bulb's meningeal lymphatic vessels, and the restoration of drainage function via intranasal VEGF-C gene delivery. [Ministry of Science and ICT]

The researchers also examined how aging affects the drainage pathway. In aged mice, the arachnoid fenestrations narrowed, surrounding meningeal lymphatic vessels decreased in number, and the channels in the cribriform plate through which lymphatic vessels and olfactory nerves pass also constricted — all of which significantly reduced cerebrospinal fluid drainage.

When the researchers administered VEGF-C, a gene that promotes lymphatic vessel growth, to the nasal mucosa of aged mice, lymphatic vessels around the nasal cavity and olfactory bulb regenerated, the drainage pathway widened, and cerebrospinal fluid drainage recovered to levels seen in young mice. The findings point to a potential non-invasive treatment strategy — delivering drugs through the nose — for degenerative brain diseases including dementia.

"This research identifies the structural cause of age-related decline in brain-cleaning function, showing that the arachnoid fenestrations, surrounding lymphatic vessels and cribriform plate channels all deteriorate together as the brain ages," Director Ko said.

Hong Sun-pyo, the senior researcher who led the study, said the team had confirmed that cerebrospinal fluid drainage impaired by aging could be restored to the level seen in young organisms. "We plan to extend this research to human tissue and develop new treatment strategies applicable to a range of degenerative brain diseases," he added.

nbgkoo@heraldcorp.com