Researchers have discovered an approach that could prevent nerve cells in the brain from deteriorating after a traumatic brain injury (TBI).

A research team including scientists with the Geriatric Research Education and Clinical Center at the Louis Stokes Cleveland VA Medical Center identified the approach for preventing nerve cell degeneration by exploring the connection between TBI and Alzheimer’s disease.

Their research, summarized earlier this year in the journal “Cell,” linked the two diseases by identifying a harmful process – acetylation of the tau protein – occurring in the brain in both conditions.

Dr. Andrew A. Pieper (standing, center, with blue suit), the senior author of the study, is a psychiatrist at the Cleveland VA. Here, he’s with his lab team at the Harrington Discovery Institute in Cleveland.

Dr. Andrew A. Pieper (standing, center, with blue suit), the senior author of the study, is a psychiatrist at the Cleveland VA. Here, he’s with his lab team at the Harrington Discovery Institute in Cleveland. (Photo courtesy of Pieper lab)

Two drugs may stop brain deterioration

Importantly, the investigators went on to identify two FDA-approved medications that could obstruct the dangerous process. They say these drugs could suggest new directions in TBI and Alzheimer’s research and treatment.

“By following through on this line of research, we hope to one day be able to tell Veterans and others who have suffered a TBI, ‘We have medicines to help your brain repair itself and recover from your injury,’” says Dr. Andrew A. Pieper.

Pieper is a VA psychiatrist and researcher, and senior author on the Cell article, titled “Reducing Acetylated Tau is Neuroprotective in Brain Injury.”

Why focus on TBI?

Traumatic brain injuries are caused by a bump, blow or jolt to the head. These types of injuries are common, with about 5 million people in the United States living with a disability after TBI. Brain injuries frequently occur during activities and events like rough contact during sports, car accidents and falls. In service members and Veterans, TBI also often follows from explosions during combat or training exercises. TBI can lead to headaches, irritability, sleep disorders, memory problems, slowed thinking and depression. These problems can turn into long-term challenges with brain function that disrupt people’s lives.

Along with factors such as aging and genetics, TBI has been found to raise the risk of Alzheimer’s disease. The reason for this association between brain injury and Alzheimer’s disease has been unknown.

With funding from VA and other sources, the scientists in Andrew Pieper’s lab at the University Hospitals’ Harrington Discovery Institute in Cleveland set their sights on solving the riddle.

“We are keenly interested in identifying the mechanistic link between TBI and Alzheimer’s disease,” Pieper says. He explains that an understanding of this fundamental issue holds great potential for helping so many people with either condition.

“In terms of Alzheimer’s disease, we can’t do anything about our genetics or stop our aging,” Pieper adds. Preventing whatever increases the risk of Alzheimer’s disease after TBI thus represents a great opportunity to meaningfully protect people from brain neuron deterioration.”

Ac-tau pinpointed as common culprit

The research project began when Dr. Min-Kyoo Shin, a senior research scientist in Pieper’s lab, decided to examine whether acetylated tau (ac-tau) was an offender in TBI. Previous studies had identified the destructive substance in brains of people with Alzheimer’s disease.

Shin’s study found a rapid elevation of the suspected substance in mice after TBI. It also showed that this modification of the tau protein was causing parts of the brain’s nerve cells called axons to degenerate. This harmed cognitive function.

“Although TBI is one of the strongest risk factors in dementia and Alzheimer’s disease, before our finding, nobody had shown how TBI may lead to this condition,” points out Shin, a first author on the Cell paper.

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By Tamar Nordenberg is a freelance writer supporting VA's Office of Research and Development (ORD)

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Published on Nov. 12, 2021

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