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 in Blast-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.