Boston University CTE Center and Brain Bank

Dr. Ann McKee is the Director of the Boston University CTE Center and a professor of neurology and pathology at the Boston University School of Medicine. Her research focuses on CTE and the late effects of neurodegeneration. Along with her colleagues, McKee has conducted several research studies involving traumatic brain injuries in sports and military situations, and the long-term effects of these injuries. While her largest project has been the formation and expansion of the VA-BU-CLF Brain Bank, McKee is also the director of several other brain banks, all of which are located in Massachusetts.[3][10]

Dr. Chris Nowinski is the co-founder and current CEO of the Concussion Legacy Foundation, an organization dedicated to the awareness and prevention of concussions in every level of sport. Concussions in American football is particularly important to Nowinski as he himself experienced a significant brain injury while playing football at Harvard University. Nowinski partnered with researchers from Boston University to create the VA-BU-CLF Brain Bank.[11]

Lisa McHale currently acts as the director of family relations for the VA-BU-CLF Brain Bank, working with families of former athletes to help them understand CTE and the mission of the Boston University CTE Center. McHale joined the Concussion Legacy Foundation in 2010, first acting as the Volunteer and Family Coordinator. McHale has personal experience with families dealing with the effects of CTE, as her husband Tom McHale, a former American football player, passed away in 2008 due to complications from the disease.[12]

Example of tau pathology in human brain

In 2009, Dr. McKee and her team of researchers from Boston University published their first CTE study. This publication discussed 47 instances of neuropathological deterioration determined to be CTE. The study involved former athletes from a wide range of sports.[4] The majority of the reported CTE cases were former boxers (85%), but the study also included cases from former American football players, soccer players, and wrestlers. The study was primarily conducted to develop a more accurate clinical presentation of CTE in the brain. By studying the brains of former athletes whose sports commonly involved blows to the head, the researchers were able to identify how CTE looked in the brain of a former athlete.[8] Through in-depth autopsies, the researchers observed the formation of proteins in the brain that caused initial brain cell decay, ultimately leading to CTE in the brain.[4]

Healthy brain (left) and brain with stage IV CTE (right)

The first major American football study conducted by the BU CTE Center involved the donated brains of 79 former NFL players. This study was released in 2015 and detailed the autopsies performed by researchers on the donated brains and brain tissue.[8][1] These examinations were performed at both the macroscopic and microscopic levels, in order to identify important neuropathological characteristics of CTE, including how the brain deteriorates over time, and the distribution of proteins in brains with CTE. Through microscopic examination, the researchers were able to confirm the role of the tau protein in CTE diagnosis, as well as other proteins that are signs of this degenerative disease.[13] This tau protein was present in each brain that was diagnosed with CTE, demonstrating its role in the development of the disease.[1]

From these post-mortem tests, researchers were able to detail the characteristics of the various stages of CTE. In the study, the Boston University researchers grouped the subjects into four distinct stages of CTE, with each stage increasing in severity. In stage I CTE, p-tau pathology can be observed in the cerebral cortex, most likely in the area between sulci. In the second stage of CTE, the tau protein is observed in multiple areas of the cerebral cortex, as the p-tau pathology begins to spread across sulci. In stage III CTE, the tau protein becomes widespread, with the greatest severity located in the frontal and temporal lobes. The p-tau groups in these regions are often concentrated in the depths of the sulci. In stage IV CTE, severe p-tau pathology is spread across all areas of the cerebral cortex and temporal lobe. In extreme cases, the tau protein calcarine cortex, which contains the primary visual cortex in the brain.[1][14] In the study, researchers noted that microscopic signs of p-tau pathology were primarily observed in subjects with Stage III and IV CTE.[1]

Two years after the Center's 2015 study, researchers from Boston University partnered with Stanford University to conduct autopsies on the brains of 202 deceased former American football players from multiple levels (high school, college, semi-pro, CFL, NFL). Recruitment for this study began in 2008, after the establishment of the VA-BU-CLF Brain Bank. After the success of the 2015 American football case study, donations to the Brain Bank grew, as the link between CTE and American football became clear. These increased donations allowed for a larger case study, which would give researchers an opportunity to paint a clearer picture of the disease in a brain.[7]

Each of the 202 deceased players had a history of brain trauma and experienced behavioral, mood, and cognitive symptoms during their lives. In addition, the most common cause of death among participants was neurodegeneration or suicide. Each brain was evaluated and CTE p-tau pathology for the brains were classified into a stage of CTE.[13] The study showed that of the 202 evaluated brains, CTE was neuropathologically diagnosed in 177 (87%), including 110 of 111 former NFL players (99%). In all cases of CTE, clusters of the tau protein were found in the cerebral cortex, consistent with earlier studies from the CTE Center. These results suggested CTE might be related to participation in football, and higher levels of play may increase the likelihood of the disease.[9]

Former New England Patriots Tight End Aaron Hernandez, Subject of the BU CTE Center

In April 2017, former New England Patriots tight end Aaron Hernandez committed suicide in a jail cell at the age of 27. Hernandez's suicide occurred just months after he was convicted of first-degree murder and sentenced to life in prison without the possibility of parole. After his death, Hernandez's brain was donated to the VA-BU-CLF Brain Bank, where Boston University researchers, led by Dr. Ann McKee, immediately performed an autopsy on the post-mortem brain.

The posthumous examination of the brain showed that Hernandez suffered from stage III CTE, which had previously only been diagnosed in former American football players who were well into their 60s before their deaths.[15] According to Dr. McKee, Hernandez's brain presented a classic case of CTE, as multiple groupings of the tau protein could be seen in frontal lobes. These p-tau deposits developed in close proximity to small blood vessels in the brain and spread to areas that control perception, memory, and emotion.[15][16]

The discovery from Hernandez's autopsy began to shed new light on the impact of CTE in American football players, as well as other athletes. The degree of the CTE present in Hernandez's brain was unprecedented for someone so young. In the autopsy report from Boston University, Dr. McKee explains that Hernandez's brain was one of the most intact specimens her team had ever examined. McKee also notes that the damage to Hernandez's brain took years to develop, and was not the symptom of one incident.[16] While the fear of CTE in American football players had grown after initial discoveries from Boston University, most of the cases featured older players who had been retired for several decades before passing away.[7] With the study of Hernandez's brain, a new push was established to attempt to find a method for diagnosing the disease in living subjects, and ultimately develop ways to treat the disease.[17]