U.S. Air Force Photo by J.M. Eddins Jr.

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Research from the Keck School of Medicine at the University of Southern California (USC) shows that damaged capillaries in the brain — independent of plaques and tangles of abnormal proteins — may set the stage for Alzheimer’s decades before memory problems emerge.

“The fact that we’re seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process,” said Berislav Zlokovic, M.D., Ph.D., and director of the Zilkha Neurogenetic Institute at the Keck School.

In healthy brains, the cells that form the walls of capillaries fit tightly together to form a barrier that keeps stray cells, pathogens, metals and other unhealthy substances from reaching brain tissue. Scientists call this the blood-brain barrier. 

In some aging brains, the seams between cells loosen, blood vessels become permeable and neurons begin to die.

Mapping blood-brain barrier

Zlokovic works closely with Arthur Toga, Ph.D., a world leader in mapping brain structure and functioning, at the Keck School.

“Brain imaging is integral to studying Alzheimer’s disease. In visualizing the blood-brain barrier in people, we actually can see and measure changes where the barrier breaks down,” Toga said. “We’ve been able to correlate greater leakage with increased cognitive decline.”

In addition, brain imaging is allowing Toga to detect changes, potentially indicative of disease, in the spaces around blood vessels in the brain. Known as perivascular spaces, they help drain fluid and metabolic waste from the brain.

Other USC scientists are also working at the intersection of blood vessels and brain health, including Diana Younan, a senior research associate in the department of preventive medicine at the Keck School. 

She studies the link between air pollution and dementia. The exact mechanism isn’t fully understood; for instance, does fine particle pollution penetrate the blood-brain barrier and infiltrate brain tissue? Is it a matter of pollution triggering inflammation?

In her recent research, Younan looked at this association and explored the protective effects of higher levels of education, physical activity and challenging work — all of which contribute to “cognitive reserve,” or resilience in the brain’s function. 

When she and her colleagues studied people exposed to fine particle pollution, they found that higher levels of cognitive reserve seemed to protect against dementia.

“Here in Los Angeles, you can’t really avoid air pollution,” Younan said. “So, if people are staying involved in mentally stimulating activities, it could decrease the risk of memory problems later on.”

Diabetes treatment protects

Daniel Nation, an assistant professor of psychology at the USC Dornsife College of Letters, Arts and Sciences, found in an observational study that untreated diabetes is associated with elevated tau pathology and risk for dementia, whereas treated diabetes is not. One theory is that diabetes treatment may keep the brain’s blood vessels healthy, staving off dementia.

“It’s clear that the medicines for treating diabetes make a difference in the progression of dementia,” Nation said. “But it’s unclear how exactly those medications slow or prevent the onset of Alzheimer’s disease, so that is something we need to investigate.”

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