Amyloid pathology fingerprint differentiates post-traumatic stress disorder and traumatic brain injury

Introduction: Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for early onset of Alzheimer's disease (AD) and may accelerate the progression rate of AD pathology. As amyloid-beta (Aβ) plaques are a hallmark of AD pathology, we hypothesized that TBI and PTSD might increase Aβ accumulation in the brain. Methods: We examined PET and neuropsychological data from Vietnam War veterans compiled by the US Department of Defense Alzheimer's Disease Neuroimaging Initiative, to examine the spatial distribution of Aβ in male veterans' who had experienced a TBI and/or developed PTSD. Subjects were classified into controls, TBI only, PTSD only, and TBI with PTSD (TBI_PTSD) groups and data were analyzed using both voxel-based and ROI-based approaches. Results: Compared to controls, all three clinical groups showed a pattern of mainly increased referenced standard uptake values (SUVR) for the amyloid tracer [18F]-AV45 PET, with rank order PTSD > TBI_PTSD > TBI > Control, and same rank order was seen in the deficits of cognitive functions. SUVR increase was observed in widespread cortical regions of the PTSD group; in white matter of the TBI_PTSD group; and cerebellum and precuneus area of the TBI group, in contrast with controls. The [18F]-AV45 SUVR correlated negatively with cerebrospinal fluid (CSF) amyloid levels and positively with the CSF tau concentrations. Conclusion: These results suggest that both TBI and PTSD are substantial risk factors for cognition decline and increased Aβ deposition resembling that in AD. In addition, both PTSD and TBI_PTSD have a different pathways of Aβ accumulation. Keywords: Traumatic brain injury, Post-traumatic stress disorder, Alzheimer's disease, Amyloid, PET, Department of Defense Alzheimer's Disease Neuroimaging Initiative (DOD-ADNI