The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features

Grant L. Iverson*, C. Dirk Keene, George Perry, Rudolph J. Castellani

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


There is tremendous recent interest in chronic traumatic encephalopathy (CTE) in former collision sport athletes, civilians, and military veterans. This critical review places important recent research results into a historical context. In 2015, preliminary consensus criteria were developed for defining the neuropathology of CTE, which substantially narrowed the pathology previously reported to be characteristic. There are no agreed upon clinical criteria for diagnosis, although sets of criteria have been proposed for research purposes. A prevailing theory is that CTE is an inexorably progressive neurodegenerative disease within the molecular classification of the tauopathies. However, historical and recent evidence suggests that CTE, as it is presented in the literature, might not be pathologically or clinically progressive in a substantial percentage of people. At present, it is not known whether the emergence, course, or severity of clinical symptoms can be predicted by specific combinations of neuropathologies, thresholds for accumulation of pathology, or regional distributions of pathologies. More research is needed to determine the extent to which the neuropathology ascribed to long-term effects of neurotrauma is static, progressive, or both. Disambiguating the pathology from the broad array of clinical features that have been reported in recent studies might facilitate and accelerate research-- and improve understanding of CTE.

Original languageEnglish (US)
Pages (from-to)17-28
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number1
StatePublished - 2018
Externally publishedYes


  • Concussion
  • neurodegenerative
  • neuropathology
  • tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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