New research from the University of Virginia has found mild head injuries can increase the risk of Alzheimer’s disease later in life – but scientists say acting quickly after injury may help reduce the risk of both Alzheimer's and other long-term brain damage.
In lab studies, researchers found that a single mild traumatic brain injury like a concussion can damage the brain’s lymphatic drainage system, the network that clears waste and harmful proteins from the brain. When that system is disrupted, Alzheimer’s-related proteins can build up faster, increasing the risk of long-term brain damage.
The research team, led by John Lukens, director of UVA’s Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases, was able to repair that drainage system within 24 hours of injury in lab mice.
They used a harmless, emptied virus shell as a delivery vehicle to carry a naturally-occurring repair protein to the brain’s protective layers. The protein helped damaged drainage vessels regrow and function properly, preventing the buildup of tau — a toxic protein linked to Alzheimer’s disease.
“By boosting the brain drainage using this growth factor that kind of fixes the pipes above the head that does the draining, that can provide a therapeutic treatment option to eliminate the risk of Alzheimer's and CTE after brain injury,” Lukens said.
Lukens said the findings suggest there may be a crucial treatment window shortly after head trauma when long-term neurological damage could be reduced, particularly for patients who require hospital care.
“One of the critical new experiments we’re going to have to do is see how far out the therapeutic window is — where it would still have a beneficial effect,” Lukens said. “Obviously it would be great if we had a larger window, but at least with this, we know that targeting those who’ve had severe brain injuries that require transport and treatment at a hospital would be the ideal population to benefit at the moment.”
The direct connection between lymphatic vessels and the brain were first identified by UVA researcher Jonathan Kipnis in 2015 and are now known to play a vital role in brain health and immune regulation. When they fail, immune cells become less effective at clearing debris, accelerating neurodegeneration.
Lukens said the research could have particular implications for veterans, as blast injuries often affect the meninges, the protective layers surrounding the brain where lymphatic vessels are located.
He said restoring brain drainage may also hold promise for people at high genetic risk for Alzheimer’s disease and could eventually be combined with existing treatments, including antibody drugs that target amyloid beta, a protein that builds up in the brains of people with Alzheimer’s.
Human trials are still years away, and Lukens said the approach is unlikely to reverse Alzheimer’s once neurons are lost. But the findings suggest it could help prevent or slow disease progression if applied early.
