According to the Centers for Disease Control and Prevention, each year 1.7 million people sustain a Traumatic Brain Injury (TBI).
By Max Wallack
Alzheimer's Reading Room
Tufts Medical Center in Boston which shows that even a single TBI (traumatic brain injury) can lead to Alzheimer’s disease.
It has been known for some time that a dysfunction of BACE1 can cause elevated levels of amyloid-beta. The enzymes involved in clearing this excess amyloid-beta has been the subject of my research for the past year. Now, it appears that a single traumatic brain injury can decrease several important proteins in the brain that apparently regulate BACE1. With a decrease in these proteins comes in increase in BACE1 that leads to increased amyloid-beta.
A post-mortem study on Alzheimer’s patients found this same relationship between several decreased proteins and increased amyloid-beta.
The text of the original newscast is below:
Single brain trauma can lead to Alzheimer's
New research using mice and post-mortem samples of brains from patients with Alzheimer's disease found that a single event of a moderate-to-severe traumatic brain injury (TBI) can disrupt proteins that regulate an enzyme associated with Alzheimer's.
The study reveals the complex mechanisms that result in a rapid and robust post-injury elevation of the enzyme, BACE1, in the brain. These results could lead to the development of a drug treatment that targets this mechanism to slow the progression of Alzheimer's disease.
"A moderate-to-severe TBI, or head trauma, is one of the strongest environmental risk factors for Alzheimer's disease. A serious TBI can lead to a dysfunction in the regulation of the enzyme BACE1. Elevations of this enzyme cause elevated levels of amyloid-beta, the key component of brain plaques associated with senility and Alzheimer's disease," first author Kendall Walker, PhD, postdoctoral associate in the department of neuroscience at Tufts University School of Medicine (TUSM), was quoted as saying.
Giuseppina Tesco, MD, PhD, of Tufts University School of Medicine (TUSM), led a research team that first used an in vivo model to see the effect of a single episode of TBI and how it could alter the brain. In the first two days following injury, levels of two intracellular trafficking proteins (GGA1 and GGA3) were reduced, and an elevation of BACE1 enzyme level was observed.
In an analysis of post-mortem brain samples from Alzheimer's patients, the researchers found that GGA1 and GGA3 levels were reduced while BACE1 levels were elevated compared to the brains of people without Alzheimer's disease, suggesting a possible inverse association.
In an additional experiment using a mouse strain genetically modified to express the reduced level of GGA3 that was observed in the brains of Alzheimer's disease patients, the team found that one week following traumatic brain injury, BACE1 and amyloid-beta levels remained elevated even when GGA1 levels had returned to normal. This suggests that reduced levels of GGA3 were solely responsible for the increase in BACE 1 levels and therefore the sustained amyloid-beta production observed seven days after injury.
"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. BACE1 enzyme levels may be stabilized when levels of the two proteins are low, likely caused by an interruption in the natural disposal process of the enzyme," Tesco, assistant professor of neuroscience at Tufts School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts, was quoted as saying.
"We found that GGA1 and GGA3 act synergistically to regulate BACE1 post-injury. The identification of this interaction may provide a drug target to 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 post-mortem brain samples from patients with moderate-to-severe traumatic brain injuries."Moderate-to-severe TBIs are caused most often by traumas that result in a loss of consciousness, such as severe falls or motor vehicle accidents. Not all traumas to the head result in a TBI.
According to the Centers for Disease Control and Prevention, each year 1.7 million people sustain a TBI. Concussions are the mildest form of a TBI and account for about 75% of all TBIs.
Studies have linked repeated head trauma to brain disease and some previous studies have linked single events of brain trauma to brain disease, such as Alzheimer's. Alzheimer's disease currently affects as many as 5.1 million Americans and is the most common cause of dementia in adults age 65 and over.
Source CBS 42 Birmingham, AL http://bit.ly/NKjYse
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Original content Max Wallack, the Alzheimer's Reading Room