Amyloid‐β and tau accumulation in traumatic brain injury: A study of Vietnam war veterans

Abstract

AbstractBackgroundTraumatic brain injury (TBI) is widely viewed as a risk factor for dementia. Since amyloid‐β and tau pathology have been reported in up to a third of individuals with TBI – even after a single TBI event – their accumulation could be a potential mechanism underlying this association. The aim of this study was to examine the relationship between TBI and amyloid‐β and tau pathology more closely and to assess whether the association between amyloid‐β and tau is influenced by TBI status.MethodA total of 102 Vietnam war veterans (79% normal cognition, 21% mild cognitive impairment; 23% amyloid‐β positive) were included from the Alzheimer’s Disease Neuroimaging Initiative Department Of Defense study. Among these individuals, 65 had a history of TBI (42 mild and 23 moderate/severe TBI) whereas 37 did not. Amyloid‐PET ([18F]florbetapir) and tau‐PET ([18F]flortaucipir) SUVRs were assessed within regions from the Schaefer atlas. For both amyloid‐PET and tau‐PET ROI‐wise and global TBI group differences were determined by ANCOVAs. Moderating effects of TBI status on the association between ROI‐wise amyloid‐PET and tau‐PET SUVRs were tested using linear regression. Analyses were adjusted for age, sex, education, clinical diagnosis, and, where applicable, global amyloid‐PET and time lag between amyloid‐ and tau‐PET scans.ResultTBI groups did not show significant increases in amyloid‐ or tau‐PET uptake compared to no‐TBI groups, neither globally nor on the ROI‐level (i.e. all p>0.05 after correcting for multiple comparisons, Fig. 1). However, we found that a history of (particularly moderate/severe) TBI was associated with a weaker relationship between amyloid‐PET and tau‐PET uptake in temporal and parietal brain regions compared to no history of TBI (Fig. 2). This effect seemed to be driven by the amyloid‐β positive group. TBI groups did not differ regarding age and APOE‐status.ConclusionWhile amyloid‐β is known to promote tau spreading in Alzheimer’s disease (AD), our results indicate that in TBI there might be a detachment of amyloid‐β and tau pathology in AD‐susceptible temporo‐parietal brain regions. This finding is supportive of the view that TBI could lead to distinct changes in the interplay of pathological proteins, potentially underlying the link between TBI and dementia.