VA-BU-CLF Brain Bank

About

The VA-BU-CLF Brain Bank is the largest tissue repository in the world focused on traumatic brain injury (TBI) and CTE. The VA-BU-CLF Brain Bank research team conducts high-impact, innovative research on chronic traumatic encephalopathy and other long-term consequences of repetitive brain trauma in athletes and military personnel. The brain bank contains more than 1,200 brains, including over 700 brains that have been diagnosed with CTE using the recently defined NINDS criteria for the diagnosis of CTE. For more information on the neuropathological diagnosis of CTE, please see The Second NINDS/NIBIB Consensus Meeting to Define Neuropathological Criteria for the Diagnosis of Chronic Traumatic Encephalopathy.

Dr. McKee and her team of neuropathologists and other investigators have published a large number of studies focused on CTE (see below).

The VA-BU-CLF brain bank:

Collects central nervous system tissue samples (brain, spinal cord and eyes) from deceased athletes to better understand the long term effects of mild traumatic brain injury (mTBI) and Chronic Traumatic Encephalopathy (CTE). Researchers at the VA-BU-CLF Brain Bank are dedicated to improving understanding of the long term consequences of mTBI and advancing the diagnosis, treatment and care and for Veterans and civilians living with mTBI and CTE.

Reports findings to caregivers in a timely fashion

Stores and distributes optimally prepared tissue to qualified researchers around the world

Shares data and other findings with other researchers

The VA-BU-CLF research team is focused on developing:

• A diagnostic test for CTE in living persons
• Genetic risk factors
• Environmental risk factors
• The importance of age at first exposure
• The roll of length of playing career
• Treatment for CTE

All publication of findings are de-identified (without name and identifiable details) unless the CTE Center has received permission from the family to publicize the subject’s participation.

Family members of deceased athletes may donate their loved one’s brain and spinal cord after their death to the VA-BU-CLF Brain Bank to be examined neuropathologically for evidence of CTE or other disorders of the central nervous system. The family member(s) will be interviewed for a history of their loved one, including their loved one’s athletic and concussion history, educational and occupational history, medical history and history of cognitive, behavioral, and mood symptoms.

For additional information, please contact:

Evan Nair by phone at 617-358-5996 or Madeline Uretsky by phone at 617-358-6027. You can reach both Evan and Madeline on their 24/7 voicemail/pager at 617-992-0615.

For questions regarding your Brain Donation Registry Card, please contact Kelly Dean of the Concussion Legacy Foundation at 857-244-0810 or [email protected]

Team

Case Studies

Pathology, the scientific study of the nature of disease and its causes, is the bedrock of medical research. Usually, before a disease can be diagnosed in living people or treated, it must be understood pathologically.

In 2009, only 51 cases of CTE had been studied pathologically and published in medical literature. By 2018, this number has risen to over 320 cases of CTE.

Much can be learned by combining pathology with a retrospective examination of the person’s life and clinical symptoms. Please review the case studies below. If the case is identified by name, the family has given explicit permission to share their story with the hope of increasing understanding of this devastating disease.

Mez J, Solomon TM, Daneshvar DH, Stein TD, McKee AC. Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player. JAMA Neurol. 2016 Mar; 73(3):353-5.View Related Profiles. PMID: 26747562; PMCID: PMC4792748; DOI: 10.1001/jamaneurol.2015.3998;.

Research & Academic Articles

 1. McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee H-Y, Kubilus CA, Stern RA. Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy following Repetitive Head Injury.  J Neuropath Exp Neurol, 2009 68(7): 709-735.

Prior to 2009, the precise immunohistochemical and pathological characterization of CTE had never been described and there was no rigorous compilation of the clinical and demographic findings. This manuscript was the first to report that the pathology of CTE was distinctive and consisted of an irregular accumulation of phosphorylated tau pathology in a perivascular and irregular pattern at the depths of the cortical sulci. She also described the involvement of the medial temporal lobe in later stages of the disease with prominent involvement of the brainstem and deep cholinergic nuclei. The neurodegeneration was latent; occurring 8-10 years after the last trauma, was very typically slowly progressive (as long as 40 years), with prominent behavioral and personality changes in addition to cognitive changes and memory loss. This paper marked the beginning of a worldwide upsurge of interest in the chronic effects of repetitive head impacts.  Although there had been several previous case reports of CTE in the literature, this was the first major academic publication that established CTE as a distinct tauopathy. The manuscript has been cited more than 1100 times and is the most cited and the most viewed manuscript at J Neuropath Exp Neurol.

 2. McKee A, Gavett B, Stern R, Nowinski C, Cantu R, Kowall N, Perl D, Hedley-Whyte E, Price B, Sullivan C, Morin P, Lee H-S, Kubilus C, Daneshvar D, Wulff M, Budson A. TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy, Journal Neuropathol Exp Neurol, 2010, 69: 918-929.

In this manuscript, McKee et al first reported the association between Amyotrophic lateral sclerosis and CTE in a 2 American football players and a boxer.

3. Goldstein LE, Fisher AM, Tagge CA, Zhang X-L,Velisek L, Sullivan JA, Upreti C, Kracht JM, Ericsson M, Wojnarowicz MW, Goletiani CJ, Maglakelidze GM, Casey N, Moncaster JA, Minaeva O, Moir RD, Nowinski CJ, Stern RA, Cantu RC, Geiling J, Blusztajn JK, Wolozin BL, Ikezu T, Stein TD, Budson AE, Kowall NW, Chargin D, Sharon A, Saman S, Hall GF, Moss WC, Cleveland RO, Tanzi RE, Stanton PK, McKee AC: Chronic Traumatic Encephalopathy inBlast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model. Sci Trans. Med. Sci Transl Med. 2012 May 16;4(134):134ra60.PMID: 22593173

The pathological consequences of blast injury on the human and mouse brain were not known in 2012. This manuscript presented the pathological features of the first series of blast-exposed military veterans and demonstrated the remarkable similarities between blast and  concussive injury. The manuscript also introduced a novel mouse model of blast injury that recapitulates memory impairments, axonal damage and pathology found in humans exposed to blast.

4. McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee H-S, Hall GF, Wojtowicz SM, Baugh CM, David O. Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC. The Spectrum of Disease in Chronic Traumatic Encephalopathy, Brain 2013, Jan;136(Pt 1):43-64. doi: 10.1093/brain/aws307.

Amyotroph Lateral Scler Frontotemporal Degener. 2013 Aug 23.

In 2013, this was the largest case series ever published on the clinical and pathological characteristics of CTE. A cohort of 85 subjects with histories of repetitive mild traumatic brain injury and 18 age-matched controls were analyzed; CTE was found in 68 subjects, including 64 athletes and 21 military veterans

cases (63%). In addition, this manuscript was essential in establishing the neuropathological diagnostic criteria, pathological staging scheme and clinicopathological correlations for CTE. This manuscript had remarkable repercussions on the rules of play in football and hockey, the management of concussions in sports, and the understanding the neurobiology of neurodegeneration after trauma.

5. Stern RA, Daneshvar DH, Baugh CM, Seichepine DR, Montenigro PH, Riley DO, Fritts NG, Stamm JM, Robbins CA, McHale L, Simkin I, Stein TD, Alvarez VE, Goldstein LE, Budson AE, Kowall NW, Nowinski CJ, Cantu RC, McKee AC. Clinical presentation of chronic traumatic encephalopathy. Neurology. 2013 Aug 21.

This manuscript described the most common clinical symptoms found in individuals diagnosed with CTE. The manuscript described three primary areas of clinical symptoms in CTE: behavioral changes including impulsivity, apathy, verbal and physical aggression, suicidality, explosivity, short fuse, and irritability; mood symptoms of depression and hopelessness and cognitive changes of memory loss, executive dysfunction and attention loss. In general, individuals who present earlier in life, mean age 35 years, tend to present with behavior or mood changes, whereas individuals who present later in life, mean age 55 years, tend to present with cognitive changes.  The more we understand the symptoms of mTBI and CTE, the better our chances of intervention in cases where individuals are suffering and may even be contemplating taking their life. 

6. Stein TD, Montenigro PH, Alvarez VE, Xia W, Crary JF, Tripodis Y, Daneshvar DH, Mez J, Solomon T, Meng G, Kubilus CA, Cormier KA, Meng S, Babcock K, Kiernan P, Murphy L, Nowinski CJ, Martin B, Dixon D, Stern RA, Cantu RC, Kowall NW, McKee AC. Beta-amyloid deposition in chronic traumatic encephalopathy. Acta Neuropathol. 2015 May 6.

7. Mez J, Solomon T, Daneshvar D, Murphy L, Kiernan P, Montenigro P, Kriegel J, Abdolmohammadi B, Fry B, Babcock K, Adams J, Bourlas A, Papadopoulos Z, McHale L, Ardaugh B, Martin B, Dixon D, Nowinski C, Cjaisson C, Alvarez V, Tripodis Y, Stein T, Goldstein L, Katz D, Kowall N, Cantu R, Stern R, McKee A. Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale & methods for the UNITE study. Alzheimers Res Ther. 2015 Oct 12;7(1):62. doi: 10.1186/s13195-015-0148-8.

8. Mez J, Solomon TM, Daneshvar DH, Stein TD, McKee AC. Pathologically confirmed chronic traumatic encephalopathy in a 25 year old former college football player. JAMA Neurology, 2016, Jan 4:1-3. doi: 10.1001/jamaneurol.2015.3998.

9. McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, Perl DP, Stein TD, Stewart W, Vonsattel JP, Tripodis Y, Alvarez VE, Bieniek KF, Crary J, Dams-O’Connor K, Gordon W and the TBI/CTE group. The First NINDS/NIBIB Consensus Meeting to Define Neuropathological Criteria for the Diagnosis of Chronic Traumatic Encephalopathy. Acta Neuropathol. 2016 Jan;131(1):75-86. doi: 10.1007/s00401-015-1515-z.

As a consensus panel funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, the preliminary neuropathological criteria established by McKee et al 2013 were used by 7 neuropathologists to evaluate 25 cases of various tauopathies, including CTE, Alzheimer’s disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen’s kappa: 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen’s kappa: 0.78) using the preliminary criteria. Based on these results, the panel refined the preliminary criteria and defined the pathognomonic lesion of CTE as an accumulation of abnormal tau in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific features of CTE recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provided the first step towards the development of validated neuropathological criteria for CTE and paved the way towards future clinical and mechanistic studies.

10. Alosco M, Mez J, Kowall N, Stein T, Goldstein L, Cantu R, Katz D, Solomon T, Kiernan P, Murphy L, Abdolmohammadi B, Daneshvar Daniel, Montenigro P, Nowinski J, Stern R, McKee AC. Cognitive Reserve as a Modifier of Clinical Expression in Chronic Traumatic Encephalopathy: A Preliminary Examination, J Neuropsychiatry Clin Neurosci. 2017 Winter;29(1):6-12. doi: 10.1176/appi.neuropsych.16030043.

11. Cherry JD, Tripodis Y, Alvarez VE, Huber B, Kiernan PT, Daneshvar DH, Mez J, Montenigro PH, Solomon TM, Alosco ML, Stern RA, McKee AC, Stein TD. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun. 2016 Oct 28;4(1):112.

12 . Mez J, Daneshvar D, Kiernan P, Abdolmohammadi B, Alvarez V, Huber B, Alosco M, Solomon T , Nowinski C, McHale L, Cormier K, Kubilus C, Martin B, Murphy L, Baugh C, Montenigro P, Chaisson C, Tripodis Y , Kowall N, Weuve J, McClean M, Cantu R, Goldstein L, Katz D, Stern R, Stein T, McKee A. Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA, 2017, in press.

Reviews
1. 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.

2. Gavett B, Stern R. McKee A. Chronic Traumatic Encephalopathy: A Potential Late Effect of Sport-Related Concussive and Subconcussive Head Trauma. Clinics in Sports Medicine, 2011 Jan; 30(1): 179-88, xi.

3. Daneshvar D, Nowinski C, McKee A, Stern R, Cantu R. Helmets and Mouth guards: The Role of Personal Equipment in Preventing Sports Related Concussions. Clinics in Sports Medicine, 2011 Jan; 30(1): 145-63, x.

4. Daneshvar D, Nowinski C, McKee A, Cantu R. The Epidemiology of Sports-Related Concussion. Clinics in Sports Medicine, Clin Sports Med. 2011 Jan; 30(1): 1-17, vii.

5. Clinical appraisal of chronic traumatic encephalopathy: current perspectives and future directions. Gavett BE, Cantu RC, Shenton M, Lin AP, Nowinski CJ, McKee AC, Stern RA. Curr Opin Neurol. 2011 Dec;24(6):525-31.

6. Stern RA, Riley DO, Daneshvar DH, Nowinski CJ, Cantu RC, McKee AC. Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. Review. PMR. 2011 Oct;3(10 Suppl 2):S460-7.

7. Baugh CM, Stamm JM, Riley DO, Gavett BE, Shenton ME, Lin A, Nowinski CJ, Cantu RC, McKee AC, Stern RA. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma.Brain Imaging Behav. 2012 Jun;6(2):244-54.

8. Stein TD, Alvarez VE, McKee AC. Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel. Alzheimers Res Ther. 2014 Jan 15;6(1):4. PMID: 24423082

9. Baugh CM, Robbins CA, Stern RA, McKee AC. Current understanding of chronic traumatic encephalopathy. Curr Treat Options Neurol. 2014 Sep;16(9):306. doi: 10.1007/s11940-014-0306-5.

10. McKee AC, Daneshvar DH, Alvarez VE, Stein TD. The neuropathology of sport. Acta Neuropathol. 2014 Jan;127(1):29-51. doi: 10.1007/s00401-013-1230-6. Epub 2013 Dec 24. PMID: 24366527

11. McKee AC, Robinson ME. Military-related traumatic brain injury and neurodegeneration. Alzheimers Dement. 2014 Jun;10(3 Suppl):S242-53. doi: 10.1016/j.jalz.2014.04.003.

12. Goldstein LE, McKee AC, Stanton PK. Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.Alzheimers Res Ther. 2014 Sep 5;6(5):64. doi: 10.1186/s13195-014-0064-3. PMID: 25478023

13. Kiernan PT, Montenigro PH, Solomon TM, McKee AC. Chronic traumatic encephalopathy: a neurodegenerative consequence of repetitive traumatic brain injury. Semin Neurol. 2015 Feb;35(1):20-8. doi: 10.1055/s-0035-1545080. PMID: 25714864

14. McKee AC, Stein TD, Alvarez VE.The Neuropathology of Chronic Traumatic Encephalopathy. Brain Pathology 2015 May;25(3):350-64. doi: 10.1111/bpa.12248.

15. Daneshvar DH, Goldstein LE, Kiernan PT, Stein TD, McKee AC. Post-traumatic neurodegeneration and chronic traumatic encephalopathy. Mol Cell Neurosci. 2015 Mar 7. pii: S1044-7431(15)00036-6. doi: 10.1016/j.mcn.2015.03.007 PMID: 25758552

16. Stein TD, Alvarez VE, McKee AC. Concussion in Chronic Traumatic Encephalopathy. Curr Pain Headache Rep. 2015 Oct;19(10):522. doi: 10.1007/s11916-015-0522-z.

17. Huber BR, Alosco ML, Stein TD, McKee AC. Potential Long-Term Consequences of Concussive and Subconcussive Injury. Phys Med Rehabil Clin N Am. 2016 May;27(2):503-11. doi: 10.1016/j.pmr.2015.12.007. Epub 2016 Feb 2. Review. PMID: 27154859

18. Blennow K, Brody D, Kochanek P, Levin H, McKee A, Ribbers G, Yaffe K, Zetterberg H. Mild traumatic brain injury, post-concussive syndrome and chronic traumatic encephalopathy. Nat Rev Dis Primers. 2016 Nov 17;2:16084.

19. Kriegel J, Papadopoulos Z, McKee AC.Chronic Traumatic Encephalopathy: Is Latency in Symptom Onset Explained by Tau Propagation?Cold Spring Harb Perspect Med. 2017 Jan 17. pii: a024059. doi: 10.1101/cshperspect.a024059

20. McKee AC, Alosco ML, Huber BR. Repetitive Head Impacts and Chronic Traumatic Encephalopathy.Neurosurg Clin N Am. 2016 Oct;27(4):529-35. doi: 10.1016/j.nec.2016.05.009.