There has been increasing attention to the relationship between football head injuries (concussions) and later life dementia. This is a rather sudden turn of events considering the NFL’s rather sorrowful behavior just a few years ago. It was not until December 2009 that the NFL acknowledged that there could be long-term damaging effects on the brain from repeated head injuries. Prior to that, league representatives—backed by claims from league-associated doctors—maintained that the results were inconclusive. At one point the party line was that these large, well-conditioned athletes were less susceptible to brain damage than lesser mortals. The history of change in events is well outlined in an article in the January 2011 New Yorker by James McGrath: “Does Football Have a Future? The N.F.L. and the concussion crisis.”
A recent article in The Wall Street Journal by Shirley Wang (“Injuries of Veterans, Football Players Are Linked to Dementia Later in Life”) adds more evidence that repeated head injuries lead to a dementia syndrome, which has been labeled as “chronic traumatic encephalopathy,” or CTE. The pathology of CTE is different from that found in Alzheimer’s disease (AD). In CTE there is a marked accumulation of the protein “tau,” which is also associated with the tangles found in AD. However, there is much less accumulation of the protein amyloid, which is found in the plaques of AD. This finding raises questions about the importance of tau in the ultimate loss of nerve cells and of memory and other areas of cognition in both CTE and AD.
It has been recognized for a long time that in AD the changes in cognition have a much higher correlation with the presence of tau-containing neurofibrillary tangles than with amyloid containing plaques. Now we think that the offending substance might not be the larger forms of tau, containing too much phosphorus (“hyperphosphoralated tau), but rather with smaller aspects of this protein, oligomers of tau. Now that CTE has been recognized, and progress made toward describing its underlying pathology, we can use this information to take advantage of some of the more recent advances in AD.
One of the most significant advances has been the ability to image the presence of amyloid in the living brain. This allows the detection of the accumulation of amyloid not only in people with AD, but also in the presymptomatic and early phases (mild cognitive impairment) of the disease. For research purposes this is valuable information. So far, attempts to image tau, though, have been unsuccessful. This may be because unlike amyloid, which is outside cells and available to the imaging markers, tau is inside cells and less exposed to similar markers. However, assuming this problem will be solved, such tau imaging would be very helpful in determining the early pathology in those exposed to repeated head injuries.
A second area of AD research has been the elucidation of “risk factor genes,” genes whose presence indicate that a person is at greater risk to get AD. No such risk factor genes have been found for CTE yet. When we do find some, we might use this information in to advise young athletes exactly what risks they are taking.
Attempts at treatment of AD have largely been focused on altering the metabolism of amyloid—either preventing its accumulation or getting rid of it. These treatment attempts have been unsuccessful so far. Now, the focus for AD is shifting to the accumulation of tau. What is learned about altering tau in AD will have application to CTE. As far as treatment for CTE, the ideal scenario would play out something like this:
(1) an athlete has repeated head injuries
(2) imaging shows the accumulation of tau, while he or she still shows no symptoms
(3) anti-tau medicine is given to prevent or reduce the chances of cognitive decline
This may sound like science fiction, but it’s much better than pretending the problem doesn’t exist.