Scientists at Korea’s Institute for Basic Science have found microscopic openings in the arachnoid membrane that let cerebrospinal fluid drain into the lymphatic system. In aged mice, a nasal gene therapy restored drainage to youthful levels.

The brain never stops making garbage. Its metabolic byproducts include proteins such as amyloid-beta, phosphorylated tau, and alpha-synuclein. When these build up abnormally, they are linked to Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. Clearing them is the job of cerebrospinal fluid, or CSF, the clear liquid that bathes the brain and spinal cord.²

Scientists have known for some time that much of this waste eventually leaves the brain through lymphatic vessels and drains into lymph nodes in the neck. But a basic question remained unanswered: how does CSF get past the arachnoid membrane, a protective barrier that separates the brain from the surrounding lymphatic system?² A team led by Director Koh Gou Young of the Center for Vascular Research at South Korea’s Institute for Basic Science (IBS), working with collaborators in Korea, Finland, and the United States, now reports that it has found the answer — tiny holes.

Doors in the barrier

The researchers discovered microscopic openings in the arachnoid membrane, which they named arachnoid fenestrations, that allow CSF to pass directly into the lymphatic vessels of the meninges, the layered membranes that wrap the brain. The findings, published in the journal Cell, map what the team describes as the most detailed pathway yet for brain waste clearance — and show that it deteriorates with age but can be functionally restored in old mice.^1,2

To find the openings, the team brought together three-dimensional whole-mount imaging, genetically engineered reporter mice, tissue clearing, scanning electron microscopy, tracer experiments, and comparative studies in nonhuman primates. They identified a specialized lymphatic network between the olfactory bulbs and the cribriform plate, the perforated bone that separates the brain from the nasal cavity. Unlike elsewhere in the arachnoid membrane, this area was dotted with openings roughly 2 to 12 micrometers across.²

Fluorescent tracers injected into the CSF gathered around the openings, crossed the arachnoid barrier, entered meningeal lymphatic vessels, passed through the cribriform plate, and continued through lymphatic vessels in the lining of the nose before draining into lymph nodes in the neck. The researchers found similar fenestrations in cynomolgus monkeys.²

“By combining three-dimensional imaging with cerebrospinal fluid tracer experiments, we identified microscopic openings in the arachnoid membrane that serve as functional gateways for CSF drainage,” said Hong Seon Pyo, a research fellow and co-first author of the study. “Finding similar structures in nonhuman primates suggests that this pathway may be broadly conserved among mammals.”²

Plugging the holes

To show the openings were genuinely essential, rather than incidental, the researchers blocked them with microspheres too large to pass through. CSF drainage to the neck’s lymph nodes dropped dramatically.² The experiment provided direct evidence that the fenestrations serve as critical exit portals — and that brain waste follows a defined lymphatic route rather than simply diffusing along olfactory nerves before reaching the nasal lymphatics.

What aging does to the drain

The team then compared young adult mice with aged ones and found deterioration along the entire route. Lymphatic vessels around the olfactory bulbs shrank markedly. The arachnoid fenestrations became both smaller and fewer. Openings in the central cribriform plate narrowed substantially. Together, those changes coincided with a sharp drop in CSF drainage.² Impaired CSF clearance has increasingly been linked to aging and neurodegenerative disease, and the study offers a concrete anatomical explanation for how that impairment might arise.

A nasal fix

Rather than delivering a treatment by penetrating the meninges, the team took a less invasive route: the nose. They administered an adeno-associated viral vector carrying the gene for vascular endothelial growth factor C, or VEGF-C, a signaling molecule that promotes lymphatic vessel growth, through the nasal cavity. The treatment selectively expanded lymphatic vessels around the olfactory bulbs and in the nasal lining.²

It did not reverse the age-related loss of fenestrations or the narrowing of the cribriform plate openings. But the expanded lymphatic network was enough to bring CSF drainage in aged mice back to levels comparable to those in young animals.²

“Using intranasal delivery of VEGF-C, we restored cerebrospinal fluid drainage in aged mice to levels comparable to young animals,” said Jin Cheolhwa, the study’s other co-first author. “We are now investigating whether this drainage pathway is disrupted in Alzheimer’s and Parkinson’s disease, and whether preserving its function could delay disease onset or progression.”²

Rethinking a barrier

The work reframes a structure anatomists have long regarded mainly as a shield. “The arachnoid has traditionally been viewed as a protective barrier surrounding the brain,” said Koh, the study’s corresponding author. “Our findings show that it also contains specialized gateways that allow cerebrospinal fluid to enter the lymphatic system. Understanding how these gateways change with aging opens new opportunities for studying brain waste clearance and neurological disease.”²

The results are in mice, with supporting anatomy in monkeys, and the link to human neurodegenerative disease remains to be tested. But by pinpointing where the brain’s drain actually is — and showing it can be unclogged — the study gives researchers a specific target in the search for ways to keep the aging brain clean.

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Notes

1. CSF clearance through arachnoid fenestrations to olfactory meningeal lymphatics. (2026). Cell. https://doi.org/10.1016/j.cell.2026.06.035
2. Institute for Basic Science. (2026, July 22). Scientists discover hidden gateways that allow the brain to clear waste [Press release]. EurekAlert! https://www.eurekalert.org/news-releases/1137060