The brain drain is real. There is a network of previously unrecognised vessels that rid the brain of unwanted extracellular fluids and other substances, including amyloid-beta – a peptide that accumulates in the brain of people with Alzheimer’s. The new discovery looks set to add to our understanding of the disease.
Jeffrey Iliff at the University of Rochester Medical Centre, New York, and his colleagues, were intrigued by the fact that there are no obvious lymphatic vessels in the brain. Among other things, the lymphatic system removes waste interstitial fluids from body tissue.
“It seemed strange that such an important and active organ wouldn’t have a specialised waste-removal system,” says Iliff.
When the researchers added fluorescent and radioactive tracers to the cerebrospinal fluid of live mice, the tracers quickly spread throughout the rodents’ brains. Using two-photon microscopy to visualise the movement in real-time, the team saw cerebrospinal fluid permeating the entire brain through ‘pipes’ surrounding blood vessels, similar to the lymphatic system that services all other organs.
The pipes work on hydraulic principles, though, and so the system breaks upon opening, making it hard to identify it outside living organisms.
Further study showed that the flow of cerebrospinal fluid ground to a halt if the researchers inactivated a second system, which helps transport water around the central nervous system and involves star-shaped cells called astroglia. That finding suggests that glial cells, which support and protect neurons, play a key role in the newly identified drainage network. Iliff’s team has named the new network the glymphatic system, in recognition of the importance of glial cells and the resemblance to the lymphatic system.
The researchers found that the glymphatic system flushes waste from the brain through large drainage veins. That waste includes 55 per cent of the amyloid-beta removed from the rodent’s brains.
“Removing waste is as vital to organ function as receiving nutrients,” says Iliff. “So the failure of the glymphatic system is probably involved in many disease states – for example, Alzheimer’s with its hallmark accumulation of amyloid-beta.”
Jose Maria Frade of the Cajal Institute in Madrid, Spain, who was not a member of the study team, says the finding heralds an exciting time in Alzheimer’s research. “Data suggests amyloid-beta is responsible for most deleterious effects of Alzheimer’s, so this ‘brain cleaning system’ could be used as a therapeutic target in individuals with Alzheimer’s disease.”
Robert Howard of King’s College London, who was also not involved in the new work, is fascinated by the discovery, but cautious about the implications for Alzheimer’s research. “It is uncertain whether treatments effective in clearing amyloid-beta in humans do anything to slow the progression of dementia,” he says. “Assuming a failure to clear amyloid-beta is at the root of Alzheimer’s disease is likely to be an oversimplification.”