Impact of moderate alcohol consumption on paired helical filament-tau propagation in C57BL/6J mice (2024)
Undergraduate: Gabriela Barros
Faculty Advisor: Sara Faccidomo
Department: Bowles Center for Alcohol Studies, UNC School of Medicine
Alzheimer’s disease (AD) is the most common form of dementia and the seventh leading cause of death worldwide. AD pathology is characterized by the aggregation of amyloid beta protein (Aβ) into extracellular amyloid plaques as well as the aggregation of microtubule associated protein tau (tau) into neurofibrillary tangles (NFTs). Heavy alcohol drinking has been identified as a possible risk factor for AD; however, the association between alcohol consumption and AD remains unclear, as do the mechanisms that underlie AD pathology. In a previous study, 3xTg-AD mice expressing the human form of pathological tau (p301L-tau) among other AD proteins underwent two-bottle home-cage alcohol drinking. Mice that consumed moderate amounts of alcohol showed considerable upregulation of p301L-tau in major brain regions. These findings suggested that alcohol exposure is associated with early onset and increased AD pathology via increased tau expression, warranting a more thorough investigation of the impact of alcohol drinking on tau propagation using a model of sporadic AD. In this study, we examined tau-specific AD-like pathology with the use of an adeno-associated virus (AAV) carrying the mRNA that codes for green-fluorescent protein (GFP)-2a-p301Ltau injected into the entorhinal cortex (EC) of C57BL/6J mice. Subsequently, mice underwent two-bottle choice home-cage drinking for four weeks to determine the impact of alcohol on AD-like tauopathy. We immunohistochemically labeled paired helical filament (PHF)-tau, an early pathological conformation of tau, and quantified both GFP and PHF-tau expression in the central EC, medial EC, and hippocampus (CA1) via light microscopy. Preliminary results show trends of increased PHF-tau expression among mice consuming alcohol in all three brain regions; however, further studies must be conducted to conclude a significant effect.