Neuropathological studies of athletes involved in contact sports have led to the McKee CTE Staging Scheme defined by four pathological stages of CTE, stages 1 (mild) to 4 (severe).^7,15 In stage 1, the pathology is localized to the superior dorsolateral and inferior frontal cortices. Here, the deposition of p-tau is largely found in the sulci of brain regions located around blood vessels.^1,2,4-6,16 In stage 2, other macroscopic changes are observed, including mild enlargement of the frontal horns of the lateral ventricles and the third ventricles, and in some cases the presence of a cavum septum pellucidum. In stage 3, there is a reduction in brain weight, mild frontal and temporal atrophy, and further enlargement of the lateral and third ventricles. Importantly, in stage 3, neurofibrillary tangles are visible in the olfactory bulb, hippocampus, entorhinal cortex, amygdala, hypothalamus and mammillary bodies. Stage 4 is characterized by more widespread regional brain pathology and includes decreases in myelinated nerve fibres and axonal dystrophy.^1,2,4-6 Overall, the pathology of CTE is well categorized at post-mortem, which allows us to target regions for in vivo neuroimaging analyses and possible in vivo diagnoses that correspond to those identified with post-mortem studies.

Hector Arciniega, Zachary H Baucom, Fatima Tuz-Zahra, Yorghos Tripodis, Omar John, Holly Carrington, Nicholas Kim, Evdokiya E Knyazhanskaya, Leonard B Jung, Katherine Breedlove, Tim L T Wiegand, Daniel H Daneshvar, R Jarrett Rushmore, Tashrif Billah, Ofer Pasternak, Michael J Coleman, Charles H Adler, Charles Bernick, Laura J Balcer, Michael L Alosco, Inga K Koerte, Alexander P Lin, Jeffrey L Cummings, Eric M Reiman, Robert A Stern, Martha E Shenton, Sylvain Bouix, for the DIAGNOSE CTE Research Project, Brain morphometry in former American football players: findings from the DIAGNOSE CTE research project, Brain, Volume 147, Issue 10, October 2024, Pages 3596–3610.

https://doi.org/10.1093/brain/awae098

https://www.lucentdiagnostics.com/wp-content/uploads/2025/08/LucentAD-p-Tau-217-White-Paper.pdf

https://www.lucentdiagnostics.com/wp-content/uploads/2025/08/LucentAD-pTau217-Provider-Sample-Test-Report-Watermarked.pdf (test results)

Stein, T. D., Montenigro, P. H., Alvarez, V. E., Xia, W., Crary, J. F., Tripodis, Y., Daneshvar, D. H., Mez, J., Solomon, T., Meng, G., Kubilus, C. A., Cormier, K. A., Meng, S., Babcock, K., Kiernan, P., Murphy, L., Nowinski, C. J., Martin, B., Dixon, D., Stern, R. A., … McKee, A. C. (2015). Beta-amyloid deposition in chronic traumatic encephalopathy. Acta neuropathologica, 130(1), 21–34. https://doi.org/10.1007/s00401-015-1435-y

Fesharaki-Zadeh A. (2023). Navigating the Complexities of Traumatic Encephalopathy Syndrome (TES): Current State and Future Challenges. Biomedicines, 11(12), 3158. https://doi.org/10.3390/biomedicines11123158

Arnett, P. (n.d.). Post-concussion symptom factors and neuropsychological outcomes in collegiate athletes. Journal of the International Neuropsychological Society. Cambridge University Press.

Chapek, K. (2020). Concussion rescue: A comprehensive program to heal traumatic brain injury. Amen Clinic Library.

Chiu, T. (2018). BrainSAVE: The 6-week plan to heal your brain from concussions, brain injuries & trauma without drugs or surgery. Lioncrest Publishing.

Collins, M. W., Iverson, G. L., Lovell, M. R., McKeag, D. B., Norwig, J., & Maroon, J. (2003). On-Field Predictors of Neuropsychological and Symptom Deficit Following Sports-related Concussion. Clinical Journal of Sport Medicine, 13(4), 222–229. https://doi.org/10.1097/00042752-200307000-00005

Collins, M., Stump, J., & Lovell, M. R. (2004). New developments in the management of sports concussion. Current Opinion in Orthopaedics, 15(2), 100–107. https://doi.org/10.1097/00001433-200404000-00010_

Cottle, J. E., Hall, E. E., Patel, K., Barnes, K. P., & Ketcham, C. J. (2017). Concussion Baseline Testing: Preexisting Factors, Symptoms, and Neurocognitive Performance. Journal of Athletic Training, 52(2), 77–81. https://doi.org/10.4085/1062-6050-51.12.21

Hainline, B. (2013). Sports-related concussion: Truth be told. Neurology: Clinical Practice.

Harvey, K. P., Hall, E. E., Patel, K., Barnes, K. P., & Ketcham, C. J. (2017). Potential factors influencing recovery from concussion in collegiate student-athletes. Journal of Concussion, 1, 205970021770708. _https://doi.org/10.1177/2059700217707084

Kati, P., Matti, V., Sanna, K., Jon, P., Tiina, L., & Laura, H. (2020). Post-Concussion Acute Signs and Reliable Cognitive Decline in a Finnish Youth Ice Hockey Sample. Archives of Clinical Neuropsychology, 36(5), 757–766. https://doi.org/10.1093/ARCLIN/ACAA108

KILLAM, C., CAUTIN, R., & SANTUCCI, A. (2005). Assessing the enduring residual neuropsychological effects of head trauma in college athletes who participate in contact sports. Archives of Clinical Neuropsychology, 20(5), 599–611. https://doi.org/10.1016/J.ACN.2005.02.001

Koskinen, S. (2020). On‐field signs of concussion predict deficits in cognitive functioning: Loss of consciousness, amnesia, and vacant look. Translational Sports Medicine.

LaBella, C. (2021). Selected issues in sport-related concussion (SRC/mild traumatic brain injury) for the team physician: A consensus statement. British Journal of Sports Medicine. BMJ._

Lewis, M. D. (2016). When brains collide: What every athlete and parent should know about the prevention and treatment of concussions and head injuries. HarperOne.

Lovell, M. R., Collins, M. W., Iverson, G. L., Johnston, K. M., & Bradley, J. P. (2004). Grade 1 or “Ding” Concussions in High School Athletes. The American Journal of Sports Medicine, 32(1), 47–54.

Lovell, M. (2003). Does age play a role in recovery from sports-related concussion? A comparison of high school and collegiate athletes. The Journal of Pediatrics.

Lovell, M. (2004). Cumulative Effects of Concussion in High School and College Athletes. Clinical Journal of Sport Medicine.

McClincy, M. P., Lovell, M. R., Pardini, J., Collins, M. W., & Spore, M. K. (2006). Recovery from sports concussion in high school and collegiate athletes. Brain Injury, 20(1), 33–39. https://doi.org/10.1080/02699050500309817

Montoya, D., Albert, J., & Lopez-Martin, S. (2023). A systematic review of neurological symptoms and brain abnormalities in SARS-CoV-2 infections. Academia Medicine, 1(1). https://doi.org/10.20935/AcadMed6110

Moser, R. (2002). Enduring effects of concussion in youth athletes. Archives of Clinical Neuropsychology.

Moser, R. (2005). Prolonged effects of concussion in high school athletes. Neurosurgery. Ovid Technologies (Wolters Kluwer Health).

Nowinski CJ, Bureau SC, Buckland ME, Curtis MA, Daneshvar DH, Faull RLM, et al. Frontiers in Neurology. 2022. Applying the Bradford Hill Criteria for Causation to Repetitive Head Impacts and Chronic Traumatic Encephalopathy; p. 13.

Nowinski, C., & Daneshvar, D. (2011). The Epidemiology of Sport-Related Concussion. Clinics in Sports Medicine.

Parry, K. D., & Batten, J. (2021). The shifting media discourse surrounding head injuries in association football. Academia Letters. https://doi.org/10.20935/AL488

Patoilo, M., Hanayik, T., Newman-Norlund, R. D., McCall, M., & Rorden, C. (2018). The Effect of Prior Concussions on Cognitive Performance in Recreational College Athletes. Anatomy & Physiology, 08(05). https://doi.org/10.4172/2161-0940.1000308

Pisker, J. (2019). Regaining memory after a second hit and other misconceptions about concussion in college athletes and non-athletes. Neurology. Ovid Technologies (Wolters Kluwer Health).

Randolph, C. (2003). Cumulative Effects Associated With Recurrent Concussion in Collegiate Football Players. JAMA.

Schneider, K. (2013). The effects of rest and treatment following sport-related concussion: a systematic review of the literature. British Journal of Sports Medicine.