Amyloid-β and tau deposition in traumatic brain injury: A study of Vietnam War Veterans

Abstract: Traumatic brain injury is widely viewed as a risk factor for dementia, but the biological mechanisms underlying this association are still unclear. In previous studies, traumatic brain injury has been associated with the hallmark pathologies of Alzheimer's disease, i.e. amyloid-beta plaques and neurofibrillary tangles comprised of hyperphosphorylated tau. Depending on the type and location of trauma, traumatic brain injury can induce spatially heterogeneous brain lesions that may pre-dispose for the development of Alzheimer's disease pathology in aging. Therefore, we hypothesized that a history of traumatic brain injury may be related to spatially heterogeneous amyloid-beta and tau pathology patterns that deviate from the stereotypical temporo-parietal patterns in Alzheimer's disease. To test this, we included 103 Vietnam War veterans of whom 65 had experienced traumatic brain injury (n = 40, 38.8% mild; n = 25, 24.3% moderate/severe). Most individuals had a history of 1 (n = 35, 53.8%) or 2 (n = 15, 23.1%) traumatic brain injury events. We included the group without a history of traumatic brain injury (n = 38, 36.9%) as controls. The majority was cognitively normal (n = 80, 77.7%), while a subset had mild cognitive impairment (n = 23, 22.3%). All participants underwent [18F]florbetapir/Amyvid amyloid-beta PET and [18F]flortaucipir/Tauvid tau-PET 39.63 +/- 18.39 years after their last traumatic brain injury event. We found no differences in global amyloid-beta and tau-PET levels between groups, suggesting that a history of traumatic brain injury does not pre-dispose to accumulate amyloid-beta or tau pathology in general. However, we found that traumatic brain injury was associated with altered spatial patterns of amyloid-beta and tau, with relatively greater deposition in fronto-parietal brain regions. These regions are prone to damage in traumatic brain injury, while they are typically only affected in later stages of Alzheimer's disease. Moreover, in our traumatic brain injury groups, the association between amyloid-beta and tau was reduced in Alzheimer-typical temporal regions but increased in frontal regions that are commonly associated with traumatic brain injury. Altogether, while acknowledging the relatively small sample size and generally low levels of Alzheimer's disease pathology in this sample, our findings suggest that traumatic brain injury induces spatial patterns of amyloid-beta and tau that differ from patterns observed in typical Alzheimer's disease. Furthermore, traumatic brain injury may be associated with a de-coupling of amyloid-beta and tau in regions vulnerable in Alzheimer's disease. These findings indicate that focal brain damage in early/mid-life may change neurodegenerative trajectories in late-life.