Decades of textbook teaching could be overturned by discovery, which might also explain links between poor health and brain disorders such as Alzheimer’s

Scientists have discovered a previously unknown link between the brain and the immune system that could help explain links between poor physical health and brain disorders including Alzheimer’s and depression.

The discovery of vessels, nestled just beneath the skull, overturns decades of textbook teaching and could pave the way for new approaches to treating brain diseases. The scientists behind the discovery described their surprise at having uncovered a major anatomical structure that until now had been entirely overlooked.

“These vessels were just not supposed to be there based on what we know,” said Jonathan Kipnis, who led the work at the University of Virginia. “I thought the body was mapped and that these discoveries ended somewhere around the middle of the last century. But apparently they have not.”

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The finding could provide a firm biological basis for growing evidence that mental health and the state of the immune system are closely intertwined.

People with diabetes, an auto-immune disease, are 65% more likely to develop dementia, a study early this year revealed. Other recent research showed that Alzheimer’s patients who suffered regular infections, such as coughs and colds, had a fourfold greater decline in memory tests during a six-month period compared with patients with the lowest infection levels.

However, it has not been clear whether the findings had real physiological underpinnings or whether they simply reflected lifestyle factors, such as diet and sedentary lifestyles, that degraded both mental and physical health independently.

“We believe that for every neurological disease that has an immune component to it, these vessels may play a major role,” said Kipnis. “In Alzheimer’s, there are accumulations of big protein chunks in the brain. We think they may be accumulating in the brain because they’re not being efficiently removed by these vessels.”

A condition like diabetes, he added, which impacts the immune system throughout the body, could also be impairing the brain’s ability to clear away the toxic proteins that are the hallmarks of the disease. The precise role of the vessels, the scientists said, remains speculation at this stage, and putting these questions to the test will be the focus of the next phase of their research.

The new anatomy is an extension of the lymphatic system, a network of vessels that runs in parallel to the body’s vasculature, carrying immune cells rather than blood. Rather than stopping at the base of the skull, the vessels were discovered to extend throughout the meninges, a membrane that envelops the brain and the spinal cord. The vessels were probably overlooked, Kipnis said, because the meninges is often regarded as the brain’s shrink-wrap packaging, rather than a piece of anatomy in its own right.

“In your medical handbook as a student, the first instruction is ‘remove meninges’,” he said. “People aren’t that interested in this area of the brain.”.

The discovery came after the scientists developed a way to mount a mouse’s meninges on a single slide so that it could be examined as a whole. After noticing vessel-like patterns in the distribution of immune cells on the slides under the microscope, they embarked on a series of tests which proved they were looking at lymphatic vessels that served the cerebral spinal fluid, the liquid that cushions the brain and spinal cord.

Preliminary experiments suggest the same anatomy exists in people, according to the research published this week in the journal Nature.

“We’re pretty confident that they’re there in humans as well,” said Kipnis.

Kevin Lee, a neuroscientist at the University of Virginia and a co-author of the paper, said: “The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks.’ There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation.”

The discovery of a new piece of brain anatomy was met with excitement by fellow scientists, although some were more cautious about the potential role of the vessels in disease.

Nick Fox, a professor of neurology at University College London, said the possibility of links between immune disease and Alzheimer’s is rapidly beoming a “hot topic and quite contentious”.

“It’s right to be cautious about findings from epidemiological studies on this where you can’t be sure about causation and correlation,” he said. “And it’s worth noting that trials of anti-inflammatory drugs [targeting the immune response] have not been successful in Alzheimer’s, but perhaps they weren’t given to patients early enough.”

The latest finding, he said, could help investigate the true nature of any link.

James Nicoll, professor of neuropathology at the University of Southampton, said: “This is likely to be an important finding in relation to understanding of infectious and inflammatory conditions of the brain provided the findings are confirmed by others and in humans.”

He was disappointed, though, that the authors had not more thoroughly verified the findings in people. “Not all of the experiments they did could be done on humans but enough could have been done to confirm the presence of similar channels,” he said.

Roxana Carare, an associate professor of cerebrovascular ageing at the University of Southampton, said: “The connections described are between the coverings of the brain and the immune system, rather than the brain itself and the immune system. The methodology is very impressive, but the findings need to be interpreted with caution in the context of diseases affecting the brain tissue itself.”