Long-term sequelae of mild-repetitive and severe traumatic brain injury: Clinical manifestations, neuropathology and diagnosis by tau PET imaging

Keisuke Takahata, Kenji Tagai, Makoto Higuchi, Masaru Mimura

Research output: Chapter in Book/Report/Conference proceedingChapter


Long-lasting neuropsychiatric sequelae of traumatic brain injury (TBI) can be devastating. Recent clinical and neuropathological studies have brought a growing awareness of the epidemiological association between TBI and neurodegenerative diseases later in life. Chronic traumatic encephalopathy (CTE), formerly known as boxer’s encephalopathy is now a widely recognized neurodegenerative disease associated with mild-repetitive TBI. CTE is characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles around small blood vessels of the cortex, typically at the sulcal depths. Late-onset neuropsychiatric sequelae are also common in the chronic stage of severe TBI. Several epidemiological studies have also shown that severe TBI is one of major risk factors of Alzheimer’s disease and other neurodegenerative diseases. Deposition of neurofibrillary tangles similar to CTE was found in the post-mortem brains of severe TBI. Overlapping long-term outcomes between mild-repetitive and severe TBI indicate that tau pathology can be regarded as a pervasive condition of TBI. Reliable neuroimaging biomarkers will be extremely useful as indicators for early interventions such as cognitive rehabilitation and social support for individuals with TBI. Positron emission tomography (PET) has been a useful tool to detect molecular pathology underlying neurodegenerative diseases. The second-generation tau tracer, 18F-PM-PBB3 (18F-APN-1607), has been indicated to enable the diagnosis of a wide range of tauopathies at the single-case level. PET imaging with 18F-PM-PBB3 is a promising neuroimaging biomarker for non-invasive method to detect tau pathology in TBI brains.

Original languageEnglish
Title of host publicationDiagnosis and Treatment of Traumatic Brain Injury
Subtitle of host publicationThe Neuroscience of Traumatic Brain Injury
PublisherElsevier Inc.
Number of pages13
ISBN (Electronic)9780128233474
ISBN (Print)9780128233481
Publication statusPublished - 2022 Jan 1


  • Biomarker
  • CTE
  • Concussion
  • Neurodegenerative disease
  • PM-PBB3
  • Positron emission tomography
  • Punch-drunk syndrome
  • Tau

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)


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