Numerous studies have shown the involvement of Traumatic Brain Injury (TBI) in increasing the risk of developing dementia and Alzheimer’s Disease (AD) with age, yet the intricate details of how TBI could increase the risk of such afflictions remain obscure. The scarcity of research in this area can be attributed partially to the lack of suitable animal models that can carry humanized versions of the genes known to pose a risk for developing AD. We used two cohorts of 6 months old mice, each consisting of 10 animals (5 males), carrying humanized versions of Amyloid Precursor Protein (APP), Tau microtubule associated protein, and either apolipoproteinE4 (APOE4) or APOE3, with the latter serving as controls. The mice received either 3 mild hits or anesthesia. The animals were scanned before and 6 months after the injury. Structural and functional images were collected on a 9.4 T animal scanner. Functional connectivity analysis revealed a global attenuation in the connectivity strengths 6 months following the injury in APOE4 mice (fig. 1). The decrease is more pronounced between the most anterior regions such as the olfactory regions and posterior regions such as the superior colliculus in the hindbrain. The most significant changes occur between the olfactory bulb and the hypothalamus, the substantia nigra and the caudate putamen, the dentate gyrus and the basomedial amygdala, the superior colliculus and the anterior olfactory nucleus, and the amygdala and the auditory cortex. Our preliminary analysis shows strong interaction between carrying APOE4 allele and diminishing long-term functional connectivity.