Single Traumatic Brain Injury Can Cause Alzheimer's: Study
A latest research suggests that a single event of trauma to brain is enough for a person to get Alzheimer's disease.
According to a research conducted on mice and utilizing post-mortem samples of brains from patients with Alzheimer's disease, a single traumatic brain Injury caused to the brain, can disrupt proteins that regulate an enzyme associated with Alzheimer's.
They study identifies the mechanisms after the injury that result in a vigorous increase of the enzyme, BACE1, in the brain. The findings could help in the development of a drug that could slow down the mechanism and delay the progression of Alzheimer's disease.
"A moderate-to-severe TBI (traumatic brain injury), 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," said first author Kendall Walker, PhD, postdoctoral associate in the department of neuroscience at Tufts University School of Medicine (TUSM) in the news release.
The research led by neuroscientist Giuseppina Tesco, MD, PhD, of Tufts University School of Medicine (TUSM), used an in vivo model for the study and found that in the first two days after the injury, levels of two intracellular trafficking proteins (GGA1 and GGA3) were reduced, and also, an elevation of BACE1 enzyme level was observed.
While analyzing the post-mortem brain samples of Alzheimer's patients, they found reduced levels of GGA1 and GGA3 and an elevated level of BACE1 compared to those who did not have the disease. This suggested 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.
The research suggests that reduced levels of GGA3 were solely responsible for the increase in BACE 1 levels and therefore the sustained amyloid-beta production observed in the sub-acute phase, or seven days, after injury, reported medical express.
"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," said 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, in the news release.
"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," she continued. "Our next steps are to confirm these findings in post-mortem brain samples from patients with moderate-to-severe traumatic brain injuries."
Alzheimer's affects as many as 5.1 million Americans at present and is the most common cause of dementia in people over the age of 65.
The findings of the study were published in The Journal of Neuroscience.