DIMENSIONS Fall 2010

Focus on Research: Traumatic Brain Injury and Alzheimer's Disease

by Murray Raskind, MD

brain drawing

What do traumatic brain injuries from blows to the head on the football field or from blast shock waves in combat in Iraq and Afghanistan have to do with Alzheimer's disease (AD)? At first, these two brain disorders may seem unrelated. After all, the brain damage from head trauma happens suddenly and afflicts people of all ages. In contrast, the brain damage from AD is an insidiously progressive process that develops over many years and afflicts people in late life. Surprisingly, however, recent research suggests that these two seemingly unrelated assaults on the brain are linked in several important ways. These links provide important clues to the cause (or causes) of AD and provide direction for new approaches to its prevention and treatment.

The first link comes from epidemiology studies of AD. These studies compare groups of people with AD to groups of people of the same age who are fortunate not to have AD. Scientists compare the life histories of these two groups, looking for differences in their past illnesses or injuries, exposure to such things as medications and industrial toxins, alcohol and tobacco use, dietary habits, and physical and mental activity. Any disorder or exposure that is found more frequently in the AD group than in the group without AD is a "risk factor" for eventually developing AD. Although it has been difficult to pinpoint such risk factors, one risk factor that has consistently emerged is a history of traumatic brain injury earlier in life that caused loss of consciousness. Indeed, traumatic brain injuries increase a person’s risk of developing AD by two-fold. It is now clear that for some people—and we do not yet know what makes people more or less susceptible to this effect—traumatic brain injury makes it easier for AD to attack the brain.

Clinical and laboratory studies have also demonstrated important links between traumatic brain injury and AD. For instance, scientists have discovered that the immediate brain responses to traumatic brain injury are remarkably similar to the brain changes in AD. Immediately after traumatic injury, the brain produces large amounts of beta amyloid—this is the very same protein that appears to be toxic to brain neurons when excessive amounts gradually accumulate over many years, forming in the amyloid plaques that are a central diagnostic feature of AD. Intriguingly, these deposits of beta amyloid into plaques do not occur immediately following traumatic brain injury. If we can figure out what prevents plaque formation despite large beta amyloid release in response to brain trauma, we may be able to prevent the formation of toxic beta amyloid deposits in AD.

The long-term brain response to traumatic injury provides another link to AD. Abnormal tau proteins in the form of neurofibrillary tangles are found in damaged brain neurons of AD patients, and they may also be a long-term consequence of traumatic brain injury. First observed in boxers who became "punch drunk" in midlife, these tau neurofibrillary tangles are increasingly being found in the brains of football players and other athletes who have suffered repeated concussions from head trauma. These traumatic brain lesions and the cognitive loss they cause, which together are referred to by doctors as "chronic traumatic encephalopathy" or "CTE," are of increasing concern to our military because of the very common blast concussions and other brain traumas suffered by our Service Members during combat in Iraq and Afghanistan. Are these young men and women at increased risk for CTE and eventual early-onset AD?

Under the leadership of University of Washington Alzheimer's Disease Research Center Associate Director Elaine Peskind, MD, we have initiated major research efforts to unravel the relationships between traumatic brain injury and AD. We are using multiple advanced brain imaging techniques, measuring brain chemicals in cerebrospinal fluid that indicate brain damage, and carefully performing neuropsychological testing to determine these relationships in Veterans who have returned from Iraq and Afghanistan, athletes who have experienced several concussions from head trauma, and others in the community who have never experienced traumatic brain injury. These studies have great promise to develop new targets for the prevention and treatment of AD.


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