Inflammasome Activation after Traumatic Brain Injury as a Risk Factor for Alzheimer’s Disease

Background Traumatic Brain Injury (TBI) is a major cause of death and disability in the United States recognized risk factor for development Alzheimer’s disease (AD). Recent studies identified that heightened inflammasome signaling plays critical role pathogenesis CNS injury release apoptosis -associated speck-like protein containing caspase recruitment domain (ASC) specks from neurons activated microglia contributes significantly to detrimental innate immune inflammatory response. This study investigated whether after TBI augmented AD-induced biochemical neuropathological outcomes loss cognitive functionality using established AD-transgenic mouse models. Method Five-month-old, 3xTg mice (with expressed APPswe, PS1M146V tauP301L genes) wild type controls were randomized underwent moderate controlled cortical impact (CCI) or served as controls. Animals allowed recover 1 hour, day, week (n = 5-8/group) assess acute pathology 12 weeks 10/group) order chronic pathology. At end respective recovery periods, sacrificed. The ipsilateral cortex tissue was processed expression by immunoblotting analysis. group assessed behavior utilizing open field (3 days), novel object recognition (2 weeks), Morris water maze (6 weeks) testing TBI. Result There statistically significant increase proteins Caspase-1, Caspase-8, ASC, IL-1β both transgenic animals. Importantly, at day TBI, increases Caspase-8 observed AD compared type. In group, behavioral showed injured had increased indicated decreased time center field, investigating object. Conclusion These findings show involved regulation response acts potential accelerant