
Your brain may contain a hidden network of vessels that helps it dispose of metabolic waste. If confirmed to be true in future studies, the discovery could transform our understanding of the brain and even reveal new therapies for conditions like Alzheimerās disease.
āIf itās true, this is huge,ā says at Oslo University in Norway, who wasnāt involved in the research. āIt would represent a paradigm shift in our understanding of all neurodegenerative diseases, but also conditions like stroke and traumatic brain injury, and our normal brain function.ā
The brain cleans itself by releasing metabolic waste into the glymphatic system, a network of channels surrounding the brainās blood vessels that feed into the lymphatic system, the bodyās drainage and filtration system.
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Most imaging studies havenāt spotted lymphatic vessels within the brain, only in its protective outer layer. But now, at Harvard University and his colleagues may have discovered a hidden network of lymphatic-like brain vessels inside the brain that connects to the glymphatic system. āThis is my most significant discovery in 30 years,ā says Ran. āIt is the dream of a scientist.ā
Team member , also at Harvard University, accidentally spotted the structures while looking for the protein beta-amyloid in brain slices from mice with an Alzheimerās-like disease. Beta-amyloid helps neurons function, but it can form toxic clumps ā a hallmark of Alzheimerās ā which may accumulate due to poor brain drainage.
When the researchers repeated the experiment in mice with and without an Alzheimerās-like disease, they consistently found dozens of the vessel-like structures in all the brain regions they sampled, including the cortex, which is involved in thinking and problem-solving; the hippocampus, which helps us form memories; and the hypothalamus, which controls sleep and body temperature.
The structures seemed to wrap around the brainās blood vessels and meningeal lymphatic vessels ā found in the outer protective layer ā suggesting they help to drain waste via the glymphatic and lymphatic systems, says Ran.
Crucially, the researchers found the tube-like formations in brain samples from someone who died with Alzheimerās disease. They have also found them in brain tissue from a person who died without the condition, according to Ran.
The team hypothesised that the structures were either a kind of lymphatic vessel, lined by cells that contain or are coated with beta-amyloid, or a form of the protein that can develop into solid fibres that seem to contribute to Alzheimerās disease, but are .
To find out, the researchers applied protein markers that highlight lymphatic vessels to brain slices from mice. These consistently stained the tube-like structures, though less strongly than known lymphatic vessels from the same animals. This prompted them to name the structures nanoscale lymphatic-like vessels, or NLVs, and conclude that they werenāt a form of beta-amyloid.
But Eide says the weak staining suggests that NLVs may not be lymphatic-like vessels, as those markers can also bind to non-lymphatic tissue. āThis is a new kind of structure weāve not known about before ā but itās unclear, what is this actually?ā
One possibility is that the structures are an artefact caused by the imaging technique used, says at the University of Southampton, UK. For instance, if the tissue sample expanded unevenly, it could lead to vessel-like fractures, he says.
This could explain why prior brain imaging studies that used more reliable techniques, such as electron microscopy, havenāt reported NLVs before, says Brown. The team plans to use this in the next few weeks, says Gu, who adds that earlier studies may have mistaken NLVs for axons, long projections from neurons that look similar.
āIām 90 per cent sure they are what we think,ā says Ran, referencing another study by the team where fluorescently tagged beta-amyloid in the brains of mice seemed to enter nearby NLVs, suggesting they do transport waste fluid.
If confirmed by other research groups, the findings could aid our understanding of Alzheimerās disease and other conditions associated with misfolded proteins, such as Parkinsonās disease. It could even lead to drugs that treat such conditions, says Brown, for instance, if dilating the vessels enhances waste fluid disposal.
bioRxiv