Brain has natural weapon to fight Alzheimer's, UTMB scientists find

A paper published this month in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, indicates the brain doesn’t have to be a victim to Alzheimer’s and suggests hope for a therapeutic treatment to help prevent dementia in people who develop the disease.

Scientists examined the postmortem brains of patients from the Oregon Brain Bank, all who died between the ages of 90 and 100. Among them, those who hadn’t had dementia but whose brains exhibited all the physiological traits of Alzheimer’s were shown to have reactivated the autophagy process, eliminating toxic proteins that cause cell damage and dementia.

“Those fortunate individuals are telling us there is a natural way for the human brain to protect itself against dementia,” said Giulio Taglialatela, a professor and director of the Mitchell Center for Neurodegenerative Diseases at the medical branch.

“The question is can we understand how they do it and can we introduce that process into everyone with Alzheimer’s disease. How do we stimulate autophagy?”

Taglialatela likens autophagy to a fire in a fireplace that burns brightly, producing energy, then leaving behind discharged matter in the form of ash that eventually is swept away.

“During their vital activity, cells produce a lot of things that must be eliminated, like the ash in the fireplace,” he said. “Very often these products are proteins.”

Some, like the tau protein, become dangerous because instead of being eliminated, they hang around in the cell, disturbing its normal vital activity. The tau protein produces the well-known tangles in the brains of people with Alzheimer’s.

“We’ve discovered that these junk proteins are capable of blocking the autophagy process; they keep accumulating and eventually lead to the demise of brain cells,” Taglialatela said. For the past 10 years, neuroscientists at the medical branch have been studying how to keep the level of toxic protein at bay, culminating in this most recent study.

The protective mechanism found in non-dementia Alzheimer’s patients, preserved autophagy that continues to reduce the tau protein, supports the future potential of autophagy-inducing strategies and therapeutic treatments, some of which Taglialatela hopes to see tested at the medical branch’s Brain Health Institute, a new center being created under his direction.

Of particular interest are the immunosuppressant agents sirolimus and tacrolimus, drugs used to prevent rejection in organ transplant patients. According to data collected by federal health providers, it appears patients using those drugs are protected from Alzheimer’s, Taglialatela said.

Studies with mice in the medical branch’s lab have demonstrated autophagy can be reignited and can eliminate the tau protein with application of these immunosuppressants.

Because humans now live longer than they used to, the prevalence of Alzheimer’s and age-related dementia place enormous strain on elderly people, on their caregivers and on the medical care system at large, amplifying the need for preventive therapeutic treatment.

“We have pushed our lifespan beyond what nature intended,” Taglialatela said. “Consequently, we have more aging bodies and aging minds and need to induce resistance to dementia. If this were a gunfight, instead of trying to hit the person shooting at me, I’d put on a bullet-proof vest, protecting me against the toxic proteins associated with Alzheimer’s.”

Taglialatela acknowledged the contributions of co-author and research developer Anna Fracassi, an expert in autophagy and a neurology postdoctoral fellow at the medical branch who will join the faculty soon, and those of other scientists on his team.

“These studies will grow significantly under the auspices of the institute,” he said. In 2021, Taglialatela’s team received the Alzheimer Award given annually by the Journal of Alzheimer’s Disease for a paper on their research into synapse function in the brain and reduced tau protein.