Brain-bank study may offer clues on ALS, related conditions

Brain-bank tissue study may offer clues on ALS—A team led by Ann McKee, MD, seen here with medical students at one of the brain banks she oversees at the Bedford (Mass.) VA Medical Center, found pathological evidence of a link between repeated head injuries—such as those experienced by athletes in contact sports such as boxing, football and hockey—and a motor neuron disease that resembles amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The results appear in the September issue of the Journal of Neuropathology and Experimental Neurology. (Photo by Frank Curran)

Repeated blows to head seen as possible cause of motor neuron disease

Researchers with VA and the Center for the Study of Traumatic Encephalopathy (CTSE) at Boston University School of Medicine have provided the first pathological evidence of a link between repeated head injuries—such as those experienced by athletes in contact sports such as boxing, football and hockey—and a disease that resembles amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The results appear in the September Journal of Neuropathology and Experimental Neurology.

For the study, Ann McKee, MD, and colleagues examined the brains and spinal cords of 12 athletes. The organs and tissues had been donated by family members to the CSTE Brain Bank, housed at the Bedford (Mass.) VA Medical Center.

The researchers found that all 12 athletes showed evidence of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease caused by repetitive trauma to the brain. The condition can result in large accumulations of tau proteins, killing cells in regions of the brain responsible for mood and emotions.

In addition to CTE, three of the athletes had been afflicted by motor neuron disease, with severe and progressive muscle weakness and deterioration for several years before their death. The brains and spinal cords from patients with CTE and motor neuron disease showed a unique pattern of deposits of tau and another protein, TDP-43. The pattern was different from that found in ALS.

Previous epidemiological research has suggested a possible tie between repetitive head trauma experienced by athletes and combat veterans and the development of ALS. But the associations are not robust, and researchers have continued to hunt for clues as to the origins of the disease. The work by McKee's team is the first to link head injuries to motor neuron disease on the basis of microscopic and chemical analysis of human tissues.

"This is the first pathological evidence that repetitive head trauma might be associated with the development of an ALS-like disease," says McKee. "Although much more work is necessary to completely understand this association, if repetitive head trauma can trigger this kind of neurodegeneration, then by studying the effects of repetitive mild brain trauma, we can learn about the early triggers of ALS and how to slow, reduce and reverse them. "

McKee and colleagues are also studying whether military troops with traumatic brain injury from blasts or other exposures on the battlefield experience the same types of effects.

ALS affects about 30,000 people in the United States. Veterans have been found to be at higher risk. The progressive disease, usually fatal, causes degeneration of nerve cells in the brain and spinal cord that leads to muscle weakness, muscle atrophy, and spontaneous muscle activity. The cause of ALS remains unknown and there is no effective treatment to date.

To learn more about McKee's work on brain injury and Alzheimer's disease, see the article in the spring 2010 issue of VA Research Today at www.research.va.gov/news/features/VA-ResearchToday.pdf.