A news release on TuftsNow is reporting a study by Tufts University School of Medicine (TUSM) that has discovered a link between traumatic brain injuries and Alzheimer’s*. Apparently, an enzyme associated with the disease, BACE1, is elevated in brains that have suffered from moderate-to-severe injury. The elevation is caused when the trauma disrupts the proteins necessary to regulate the BACE1 enzyme. The proteins under stipulation are two intracellular trafficking proteins: GGA1 and GGA3. When the amount of these proteins is decreased, BACE1 appears to increase.
The experiment was performed by neuroscientist Giuseppina Tesco, MD, PhD, of TUSM and her research team. They first used living mice and observed what effects a single traumatic brain injury had on the them. This is where they observed the aforementioned rise in BACE1.
“Elevations of this enzyme cause elevated levels of amyloid-beta, the key component of brain plaques associated with senility and Alzheimer’s disease,” said Kendall Walker, PhD, postdoctoral associate in the department of neuroscience at TUSM.
Then, the team studied postmortem samples from the brains of Alzheimer’s victims. Similarly to the mice, these brains saw increased levels of the BACE1 enzyme. With the bridge from BACE1 to amyloid-beta complete, the question of which protein’s disappearance allows for higher levels of BACE1 still remained. To isolate if one or both were the cause, experimenters used a “mouse strain genetically modified to express the reduced level of GGA3 that was observed in the brains of Alzheimer’s disease patients.” They found that when GGA1 levels returned to normal, BACE1 and amyloid-beta levels were still elevated. These findings suggest that the lack of GGA3 protein is the cause of the rise in BACE1 levels.
“When the proteins are at normal levels, they work as a clean-up crew for the brain by regulating the removal of BACE1 enzymes and facilitating their transport to lysosomes within brain cells, an area of the cell that breaks down and removes excess cellular material,” explained Tesco.
Now, you may ask, where do we go from here? Well, the team hopes their findings will lead to improved medication that will “therapeutically regulate the BACE1 enzyme and reduce the deposition of amyloid-beta in Alzheimer’s patients.”
“Our next steps are to confirm these findings in postmortem brain samples from patients with moderate-to-severe traumatic brain injuries,” Tesco added.
A recent attempt was made at a new drug for Alzheimer’s, but it failed in trial experiments. Existing drugs merely fight off symptoms of the disease, but nothing has yet been able to attack the underlying causes. Perhaps the research done by Tesco and her colleagues will eventually pave the way for such a medication.
*A traumatic brain injury (TBI) is not your everyday bump to the head. The most common TBI is a concussion. A TBI is obviously not the only cause of Alzheimer’s disease, which affects 5.1 million Americans today. But, the research has shown that the physiological side effects of serious brain injuries have shed light on some of the biological inner-workings of the disease.
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