Description Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease likely marked by widespread accumulation of tau protein in the brain. CTE is thought to result from repetitive brain trauma, including repetitive concussions and even repetitive subconcussive blows to the head, the latter not causing concussion or other obvious symptoms. CTE has been observed most often in professional athletes who are involved in contact sports (e.g., boxing, American football) and who have been subjected to repetitive blows to the head. CTE has also been diagnosed at autopsy in individuals as young as 17, and in contact sport athletes who only played sports through high school or college. In addition, CTE has been observed in non-athletes who have experienced repetitive brain trauma, including people with epilepsy, developmentally disabled individuals with head banging, and victims of domestic violence or other physical abuse. More recently, CTE has been confirmed at autopsy in soldiers with histories of repetitive brain trauma returning from Iraq and Afghanistan. It is important to note, however, that the diagnosis of CTE is one that is confirmed at this time by autopsy and all such confirmed cases have had a history of repetitive brain trauma. This suggests that repetitive brain trauma is a necessary condition for the process that eventually leads to neurodegeneration. Classification and Symptoms The symptoms of CTE begin years or even decades following exposure to repetitive blows to the head and include changes in thinking, mood, and behavior. As the disease progresses, it can lead to dementia. Symptoms associated with CTE are classified according to whether problems or changes are observed in thinking, mood, or behavior. Symptoms in these areas, as noted previously, are usually diagnosed years or even decades after repetitive brain trauma when the neurodegeneration has progressed to the point that changes in thinking, mood, or behavior begin to interfere with daily functioning. Changes in all three symptom areas can be mild at first but progress over time to a more severe form of the disease, with dementia typically evident in all advanced cases of CTE. Problems with thinking or cognition involve difficulties with learning, memory, and what is known as executive functioning, or the ability to connect experiences, memories, and behaviors. Mood changes often involve problems with depression, irritability, loss of motivation, or suicidal thinking or behavior. Behavioral changes are typically seen as problems with impulse control which can lead to aggressive or violent behaviors, or problems with substance abuse. Genetics At this point the underlying genetics of CTE are unknown. However, not everyone with a history of repetitive brain trauma develops CTE, suggesting that there may be a genetic susceptibility in individuals who go on to develop the disease. Currently, as noted previously, CTE can only be diagnosed from histology studies of brain tissue from those who are deceased. However, there appears to be a build up of something known as hyperphosphylated tau protein that is also observed in Alzheimer’s patients, although some researchers believe that the there is more tau protein in the deep sulci and less amyloid-beta plaques than are observed in Alzheimer’s disease. Also, and of particular note, all of those diagnosed with CTE at autopsy evinced a build up of tau proteins in the brain. While genes may play a role, to-date it remains a mystery why some individuals with repetitive brain trauma from such activities as sports-related concussions from professional football will go on to develop neurodegenerative disease presumed to be CTE and why others do not. We believe one factor associated with why some are affected and others are not may be related to genes, and studies are now investigating the possible role of a genetic predisposition based on carrying the apolipoprotein E (APO E) gene, which is carried on chromosome 19 and comes in several forms, one of which is APOE4, where having the double allele is a risk factor for Alzheimer’s disease. Forty percent of those with Alzheimer’s disease have this type of allele, and thus it may be a risk factor for CTE, although the post-mortem findings suggest that the amyloid beta plaques observed in the deceased brains of those who suffered from Alzheimer’s disease, are not reported to such an extent in the deceased brains of those confirmed cases of CTE at autopsy. Having the APOE4 allele may also be associated with why some football players go on to develop neurodegenerative diseases while others do not. More research, however, is needed to make these determinations. Another area of investigation that is promising is to examine an aggregate of tau genes to determine whether or not having a particular genetic profile will lead one to being more susceptible to CTE than others who do not have such a genetic profile. Work by our laboratory, in collaboration with researchers at Boston University, is examining both APOE4 and an aggregate tau risk gene score to determine predisposing factors. The genetic susceptibility for brain tau is derived from genome wide association studies based on thousands of healthy aging individuals. Here research is important as we cannot prevent disease until we can detect, or diagnosis the disease, and understand further some of the risk factors and neurobiological underpinnings that may change over time. Being able to follow the course of brain changes using more advanced imaging technology as well as combining this with information from genetics may help us to determine who is at most risk for potential permanent brain changes versus those who recover following rest. Such an approach is likely to lead to a better understanding of the genetic markers indicating risk for CTE. More research will help to address these issues. Today and the Future CTE, like most other neurodegenerative diseases, can only be definitively diagnosed at autopsy (post-mortem). Until there is an accurate marker for CTE in living individuals, it will not be possible to examine incidence and prevalence of CTE, characterize underlying structural and physiological changes, determine genetic and other risk factors, or conduct clinical trials for treatment and prevention. Our group, in conjunction with researchers at Boston University, has been conducting research on potential biomarkers for the diagnosis of CTE in living individuals. However, the most accurate biomarker of tau accumulation in the brain would be a PET radiotracer, or ligand, that could specifically bind to tau in the living brain. Now, for the first time, it is possible to investigate tau pathology in living humans using a newly developed tau ligand, initially developed by Siemens and now owned by Avid Radiopharmaceuticals. Our group has begun studies using the PET tau radiotracer which will be among the first human brain tau imaging studies, and the first ever, aside from one case study, to investigate tau deposition in the brains of living subjects with presumed CTE. In these studies we are also using state of the art structural and magnetic resonance diffusion measures, as well as magnetic resonance spectroscopy (MRS) measures, to investigate other brain imaging markers that might correlate with PET tau findings, in order to develop additional safe and cost-effective biomarkers of CTE. Helpful Resources. Below are several links that may be helpful in understanding what is Chronic Traumatic Encephalopathy (CTE). We encourage you to follow up on the knowledge provided in these links. Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease likely marked by widespread accumulation of tau protein in the brain. CTE is thought to result from repetitive brain trauma, including repetitive concussions and even repetitive subconcussive blows to the head, the latter not causing concussion or other obvious symptoms. CTE has been observed most often in professional athletes who are involved in contact sports (e.g., boxing, American football) and who have been subjected to repetitive blows to the head. CTE has also been diagnosed at autopsy in individuals as young as 17, and in contact sport athletes who only played sports through high school or college. In addition, CTE has been observed in non-athletes who have experienced repetitive brain trauma, including people with epilepsy, developmentally disabled individuals with head banging, and victims of domestic violence or other physical abuse. More recently, CTE has been confirmed at autopsy in soldiers with histories of repetitive brain trauma returning from Iraq and Afghanistan. It is important to note, however, that the diagnosis of CTE is one that is confirmed at this time by autopsy and all such confirmed cases have had a history of repetitive brain trauma. This suggests that repetitive brain trauma is a necessary condition for the process that eventually leads to neurodegeneration. The symptoms of CTE begin years or even decades following exposure to repetitive blows to the head and include changes in thinking, mood, and behavior. As the disease progresses, it can lead to dementia. Symptoms associated with CTE are classified according to whether problems or changes are observed in thinking, mood, or behavior. Symptoms in these areas, as noted previously, are usually diagnosed years or even decades after repetitive brain trauma when the neurodegeneration has progressed to the point that changes in thinking, mood, or behavior begin to interfere with daily functioning. Changes in all three symptom areas can be mild at first but progress over time to a more severe form of the disease, with dementia typically evident in all advanced cases of CTE. Problems with thinking or cognition involve difficulties with learning, memory, and what is known as executive functioning, or the ability to connect experiences, memories, and behaviors. Mood changes often involve problems with depression, irritability, loss of motivation, or suicidal thinking or behavior. Behavioral changes are typically seen as problems with impulse control which can lead to aggressive or violent behaviors, or problems with substance abuse. At this point the underlying genetics of CTE are unknown. However, not everyone with a history of repetitive brain trauma develops CTE, suggesting that there may be a genetic susceptibility in individuals who go on to develop the disease. Currently, as noted previously, CTE can only be diagnosed from histology studies of brain tissue from those who are deceased. However, there appears to be a build up of something known as hyperphosphylated tau protein that is also observed in Alzheimer’s patients, although some researchers believe that the there is more tau protein in the deep sulci and less amyloid-beta plaques than are observed in Alzheimer’s disease. Also, and of particular note, all of those diagnosed with CTE at autopsy evinced a build up of tau proteins in the brain. While genes may play a role, to-date it remains a mystery why some individuals with repetitive brain trauma from such activities as sports-related concussions from professional football will go on to develop neurodegenerative disease presumed to be CTE and why others do not. We believe one factor associated with why some are affected and others are not may be related to genes, and studies are now investigating the possible role of a genetic predisposition based on carrying the apolipoprotein E (APO E) gene, which is carried on chromosome 19 and comes in several forms, one of which is APOE4, where having the double allele is a risk factor for Alzheimer’s disease. Forty percent of those with Alzheimer’s disease have this type of allele, and thus it may be a risk factor for CTE, although the post-mortem findings suggest that the amyloid beta plaques observed in the deceased brains of those who suffered from Alzheimer’s disease, are not reported to such an extent in the deceased brains of those confirmed cases of CTE at autopsy. Having the APOE4 allele may also be associated with why some football players go on to develop neurodegenerative diseases while others do not. More research, however, is needed to make these determinations. Another area of investigation that is promising is to examine an aggregate of tau genes to determine whether or not having a particular genetic profile will lead one to being more susceptible to CTE than others who do not have such a genetic profile. Work by our laboratory, in collaboration with researchers at Boston University, is examining both APOE4 and an aggregate tau risk gene score to determine predisposing factors. The genetic susceptibility for brain tau is derived from genome wide association studies based on thousands of healthy aging individuals. Here research is important as we cannot prevent disease until we can detect, or diagnosis the disease, and understand further some of the risk factors and neurobiological underpinnings that may change over time. Being able to follow the course of brain changes using more advanced imaging technology as well as combining this with information from genetics may help us to determine who is at most risk for potential permanent brain changes versus those who recover following rest. Such an approach is likely to lead to a better understanding of the genetic markers indicating risk for CTE. More research will help to address these issues. CTE, like most other neurodegenerative diseases, can only be definitively diagnosed at autopsy (post-mortem). Until there is an accurate marker for CTE in living individuals, it will not be possible to examine incidence and prevalence of CTE, characterize underlying structural and physiological changes, determine genetic and other risk factors, or conduct clinical trials for treatment and prevention. Our group, in conjunction with researchers at Boston University, has been conducting research on potential biomarkers for the diagnosis of CTE in living individuals. However, the most accurate biomarker of tau accumulation in the brain would be a PET radiotracer, or ligand, that could specifically bind to tau in the living brain. Now, for the first time, it is possible to investigate tau pathology in living humans using a newly developed tau ligand, initially developed by Siemens and now owned by Avid Radiopharmaceuticals. Our group has begun studies using the PET tau radiotracer which will be among the first human brain tau imaging studies, and the first ever, aside from one case study, to investigate tau deposition in the brains of living subjects with presumed CTE. In these studies we are also using state of the art structural and magnetic resonance diffusion measures, as well as magnetic resonance spectroscopy (MRS) measures, to investigate other brain imaging markers that might correlate with PET tau findings, in order to develop additional safe and cost-effective biomarkers of CTE. Below are several links that may be helpful in understanding what is Chronic Traumatic Encephalopathy (CTE). We encourage you to follow up on the knowledge provided in these links.
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