Alzheimer’s, ALS and Concussions: Connecting the Dots

In what one day may be recognized as a melding of epidemiology and medical imaging, researchers are associating human conditions once viewed as unavoidable or natural consequences of American life as diseases with commonalities that can be seen and measured in the living brain. It is a transformation I have lived through from the beginning, remembering how my grandmother’s senility was viewed as an inevitable consequence of age; how those rooted in that perception mispronounced Alzheimer’s disease as “old timer’s disease;” how coaches — and parents — joked about high school players getting their “bells rung” in football; and how those impacts are now viewed as concussions.

In September it was reported in the peer reviewed journal Neurology that pro football players may have up to four times higher risk of death from Alzheimer's and Lou Gehrig's disease (ALS). Last week the American Journal of Geriatric Psychiatry published medical images online showing proteins, called tau proteins, often found in elderly patients with Alzheimer’s disease but in this case present in the brains of living NFL players (“Study First to Image Concussion-Related Abnormal Brain Proteins in Retired NFL Players,” http://www.itnonline.com/article/study-first-image-concussion-related-abnormal-brain-proteins-retired-nfl-players). Previous studies had shown that pro athletes in contact sports are at risk of developing chronic traumatic encephalopathy (CTE), a degenerative condition associated with accumulation of tau protein.

Brick by metaphorical brick, researchers are building a road to understanding brain disease and medical imaging is lighting the way. University of California, Los Angeles (UCLA) researchers used a positron emission tomography (PET) biomarker, ¹⁸F-FDDNP (2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile), which binds to deposits of amyloid plaques and neurofibrillary tau tangles, the hallmarks of Alzheimer’s disease, to look at the brains of NFL players. Compared to healthy control subjects, these athletes had elevated levels of FDDNP in the amygdala and subcortical regions of the brain, regions that control learning, memory, behavior and emotions. Players who had more concussions had higher ¹⁸F-FDDNP levels on PET scans.

The connection between football and the risk of death due to neurodegenerative disease came from a study by the National Institute for Occupational Safety and Health (NIOSH) in Cincinnati, published online in Neurology (http://www.neurology.org/content/early/2012/09/05/WNL.0b013e31826daf50.abstract), which looked at 3,439 NFL players. Of the 334 who died, seven had Alzheimer's disease and seven had ALS — four times the rate for the general population.

“While CTE is a separate diagnosis, the symptoms are often similar to those found in Alzheimer's, Parkinson's and ALS, and can occur as the result of multiple concussions," said Everett J. Lehman, author of the NIOSH study.

The work by NIOSH and UCLA researchers so far has limited practical application. It is aimed at understanding what is happening in the brains of injured athletes and whether those changes share an etiology with neurodegenerative diseases. Through their research, however, may come the means that allow early detection of disease before symptoms occur and possibly the means to prevent those diseases altogether. 

Some of this understanding may come from processes developed more than a century ago by John Snow, M.D., the father of epidemiology. In the mid-1800s, Snow hypothesized that polluted water containing a poison that had the ability “to multiply itself by a kind of growth” in the digestive tract was the underlying cause of cholera. This ran counter to the accepted belief that cholera was due to noxious gases, called miasmas. Snow traced cholera outbreaks in London to polluted wells by meticulously linking victims to where they lived and what they did. Snow died not knowing that the poison he hypothesized was a bacillus, Vibrio cholera, isolated and cultured in 1884 by Robert Koch. 

Today researchers are pursuing tau protein to better understand what is happening in the brains of injured athletes, having visualized its existence with PET in their brains and those of patients with diseases presenting with similar symptoms.

Who knows where it will lead.