Boston University Center for the Study of Traumatic Encephalopathy (CSTE)

Boston University Center for the Study of Traumatic Encephalopathy (CSTE): A Multidisciplinary Research Initiative into Chronic Traumatic Encephalopathy and the Long- Term Effects of Repetitive Brain Trauma

In September 2008, a multidisciplinary research initiative was established at Boston University School of Medicine (BUSM) to examine Chronic Traumatic Encephalopathy (CTE) and the long-term effects of repetitive concussive and subconcussive brain trauma in athletes. This new initiative, called the Center for the Study of Traumatic Encephalopathy, is a collaborative effort between researchers at BUSM, the Department of Veterans Affairs (VA), and the non-profit Sports Legacy Institute.

CTE, also referred to as dementia pugilistica (or punch drunk) is a progressive, neurodegenerative disease that eventually leads to dementia. Although it had previously been observed in boxers, in recent years, CTE has been shown to exist in other athletes, such as football players. Prior to September 2008, however, the specific neuropathology, risk factors, clinical presentation and course, and biomarkers had never been investigated in a rigorous fashion. The goal of CSTE research is to develop an in vivo diagnostic test for CTE and, ultimately, effective treatment and a cure.

The CSTE received initial start-up funding from the BU School of Medicine (including the departments of Neurology, Neurosurgery and Pathology), the BU School of Public Health’s Health and Disability Research Institute, and the VA GRECC program. The initial research goals of the CSTE were:(1) To create a brain donation registry for living athletes (active and retired) who wish to donate brain tissue after death and participate in annual telephone interviews throughout their life; (2) To collect preliminary data on clinical and genetic characteristics of CTE, as well as to examine potential biomarkers (e.g., neuroimaging, measures of proteins and neurotransmitters in cerebrospinal fluid) of the disease; (3) To determine the neuropathological characteristics of CTE in athletes by creating a brain bank (at the Bedford VA Medical Center) of tissue harvested from donors in the registry, as well as from donors whose families agree to brain donation after death, in cases where the athlete was not part of the registry; and (4) To determine the clinico-pathological correlations of CTE by comparing the clinical and brain trauma histories of athletes with the severity and distribution of the neuropathological findings.

In the two and a half years since its establishment, the CSTE has obtained additional grant funding from the National Institute on Aging and from the National Operating Committee on Standards for Athletic Equipment (NOCSAE). The VA CSTE Brain Bank currently has more than 70 brains, the majority from deceased football players. There are now more than 360 current or retired athletes (professional and amateur) who enrolled in the brain donation registry. Preliminary neuroimaging data have recently been collected from former athletes, with colleagues at the Brigham and Women’s Hospital in Boston. Additional grant applications are currently under review and being developed to fund future extensive studies of CTE, eventually leading to an understanding of the specific additional risk factors for the disease as well as developing treatments and, ultimately, a cure for CTE. The CSTE also has expanded its focus to include research on the long-term effects of repetitive brain trauma and exposure to blast injury from improvised explosive devices in military service members and Veterans. There are currently the brains of 14 veterans in the VA CSTE Brain Bank. The BU CSTE is the only research center in the world completely devoted to the study of CTE.

To date, CTE has been found in the brains of 14 of 15 deceased professional football players examined by Dr. McKee. CTE also was found in the first and only two former NHL hockey players examined by the Center. And, CTE has been found in other athletes, including those without any professional experience, and in individuals as young as 18 years. Additional research from the BU CSTE suggests that some cases of CTE can be associated with a motor neuron disease, this new neuropathological disease is termed Chronic Traumatic Encephalomyelopathy (CTEM). The occurrence of CTEM suggests that some instances of clinically diagnosed motor neuron disease or Amyotrophic Lateral Sclerosis (ALS) can be triggered by repetitive brain trauma.

BU CSTE findings have played a major role in significant changes to the game of football, including several changes to the rules of the National Football League (NFL). Both the NFL and the NFL Players Association have publicly supported the research, and have encouraged active and retired players to participate in CSTE studies. In 2010, the NFL made a $1million unrestricted gift to BU to support CSTE research. In addition to professional football, BU CSTE research has played a role in major changes to other sports at all levels of play, from professional to youth.

References: McKee, A.C., Cantu, R.C., Nowinski, C.J., Hedley-Whyte, E.T., Lee, H.S., Kubilus, C.A., Gavett, B.E., Romero, R., Budson, A.E., Ryu, H., Santini, V.E., & Stern, R.A. (2009). Chronic Traumatic Encephalopathy in athletes: Progressive tauopathy following repetitive concussion. Journal of Neuropathology and Experimental Neurology, 68¸709-735.

McKee, A.C., Gavett, B.E., Stern, R.A., Nowinski, C.J., Cantu, R.C., Kowall, N.W., Perl, D., Hedley- Whyte, E.T., Price, B., Sullivan, C., Morin, P., Lee, H.S., Kubilus, C.A., Daneshvar, D., Wulff, M., & Budson, A.E. (2010). TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. Journal of Neuropathology and Experimental Neurology. 69, 918-929. Authors' reply: McKee AC, Budson AE, Gavett BE, Stern RA, Daneshvar D, Nowinski CJ, Cantu RC, Kowall NW, Perl DP, Hedley-Whyte ET. J Neuropathol Exp Neurol. 2011 Jan; 70(1): 98-100. Gavett, B.E., Stern, R.A., & McKee, A.C. (2011). Chronic Traumatic Encephalopathy: A potential late effect of sport-related concussive and subconcussive head trauma. Clini cs in Sports Medicine, 30, 179-188. Gavett, B, Stern R, Cantu R, Nowinski C, McKee A. Mild traumatic brain injury: A risk factor for neurodegeneration, Alzheimer's Research and Therapy, 2010, Jun 25; 2(3): 18. http://www.bu.edu/cste/news/academic-articles/

revised April 29, 2011