Traumatic Brain Injury and Alzheimer's Disease Biomarkers: A Systematic Review of Findings from Amyloid and Tau Positron Emission Tomography

Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of β-amyloid (Aβ) and/or tau to examine individuals with a history of TBI who are at increased risk for AD due to age. A comprehensive literature search was conducted on January 9, 2023, and 26 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about participants' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both Aβ and tau, results were widespread but inconsistent. The regions that showed the most compelling evidence for increased Aβ deposition were the cingulate gyrus and cuneus/precuneus. Evidence for elevated tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions in both Aβ- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older individuals at risk for AD.