Around 6 million Americans were affected by Alzheimer’s disease (AD) in 2023 and this number is projected to triple by 2060. The subset of population who are 65 and older are the most vulnerable to develop AD/Alzheimer’s disease related disease (ADRD) and results from the 2021 National Survey on Drug Use and Health stated that 6.7 million adults in this age range indulged in heavy alcohol drinking. This emphasizes the need to research lifestyle risk factors such as alcohol consumption and its effect on AD. Prior research on the impact of alcohol on AD was with 3x-Tg-AD transgenic mouse model, which expressed human Tau-P301L (huTau), amyloid precursor protein, and human presenilin. We found that alcohol consumption led to early onset and increased expression of pathological huTau protein (anti-AT8) in the hippocampus, but it was unclear how alcohol specifically altered the propagation of Tau pathology throughout the brain. Using Tau seeding via the AAV-eGFP-2a-huTau-P301L, we were able to isolate the impact of alcohol on Tauopathy and distinguish viral ‘donor’ Tau cells from ‘recipient’ Tau-positive cells. AAV-eGFP-2a-huTau-P301L was microinjected into the entorhinal cortex and mice were subsequently exposed to alcohol via an ethanol chamber or 2- bottle choice protocol and achieved physiologically relevant blood alcohol levels. Staining of Tau13 confirmed that the AAV-eGFP-2a-huTau-P301L was able to express donor and recipient huTau in wild-type mice. Immunohistochemistry showed cell to cell spread of huTau in both the cell bodies and axons of a neuron; additional research will examine ethanol’s impact on Tau propagation.
J S Kim (Sat,) studied this question.