Experimental evidence that brain trauma is an environmental risk factor for Alzheimer's
(Philadelphia, PA) -- Researchers at the University of Pennsylvania School of Medicine have shown -- for the first time in an animal model -- that Alzheimer's disease-like pathology is triggered in the brain following head trauma.
Indeed, the team of Penn scientists has determined that the biochemical process that leads to the development of plaques in brain-injured animals mirrors the plaque-forming process in the brains of Alzheimer's patients. This finding supports previous epidemiological evidence that brain trauma in humans increases the risk for developing Alzheimer's disease later in life. The researchers' work is being published in the September issue of the Journal of Neuropathology and Experimental Neurology.
This study points to the importance of increased awareness about brain-trauma prevention -- especially in the form of preventable injury. "Our study suggests that even moderate brain injury resulting from a tremendous change-in-velocity can cause axonal damage sufficient to launch an insidiously progressive degenerative process," said Douglas H. Smith, MD, lead author and associate professor of neurosurgery at Penn. Given that head trauma is the only known environmental risk-factor for the development of Alzheimer's disease, the researchers suggest that society renew its commitment to better educate citizens about the specific risk-reduction behaviors that can be used to prevent head trauma or mitigate its devastating effects. These behaviors include the wearing of seat belts when driving an automobile and the wearing of helmets when riding a motorcycle or bicycle.
Diffuse Axonal Injury (DAI) Replicated
Using anesthetized pigs, the researchers duplicated the same type of head trauma that is frequently sustained by individuals in automobile accidents. In the experiment, injury was produced from a forced and very rapid acceleration/deceleration of the animal's head without impact -- a type of non-impact injury that occurs quite often in car crashes. "We were able to show that such injury is enough to cause microscopic damage throughout the brain that, in turn, initates a cascade of biochemical events that leads to the subsequent formation of Alzheimer's-like plaques," explained Smith.
Despite the brain's built-in elasticity to help shield it from damage, the scientists found that their induced injury was sufficient to produce an immediate break in the nerve fibers (axons) connecting neurons -- much like would occur if one were to stretch a cooked spaghetti noodle until it finally snapped apart. This type of instantaneous, inertial damage -- known as diffuse axonal injury, or DAI -- is seen frequently in victims of mild to severe head trauma.
The researchers further observed that the damaged axons produced A-beta, a sticky-like substance that helps sets the stage for the subsequent development of Alzheimer's-like plaques. (The investigators have surmised that the production of A-beta in trauma results from the action of a still-unidentified protease, or converter protein; and that this protease -- when identified -- may correspond to the one believed to activate the parallel neurodegenerative process found in Alzheimer's disease.)
From these observations, the scientists have concluded that there is a link between brain trauma and the initiation of a neurodegenerative Alzheimer's-like process ... a long-term process that can take many, many years to unfold in humans.
Potential Clinical Application
The study also lays the scientific foundation for the further investigation into the neurodegenerative process so that appropriate therapeutic agents may be developed to slow or block the process resulting from head injury. "This study adds to the body of knowledge that might aid us in the development of an anti-plaque-making compound," adds Smith.
The study was funded, in part, by grants from the National Institutes of Health.
To contact Dr. Smith directly:
From August 25 to 28, Dr. Douglas Smith can be reached directly at his vacation residence: (508) 778-0138. He will be travelling from August 29 to 30; and is expected back in his office on Tuesday, August 31. His office number is (215) 898-0881.