ADAD: Alcohol Disorder & Alzheimer Disease

Alcohol Dependence Exacerbates Alzheimer’s Disease Pathology in Mice

Alzheimer’s Disease (AD) is a neurodegenerative disorder that poses irreversible damage on memory, cognition, and behavior. AD progression is associated with the accumulation of Amyloid-Beta (AB) and Tau neurofibrillary tangles in the Central Nervous System. Given its multifactorial onset and progression, alcohol use is suspected to stimulate mechanisms of AD. This is supported by previous behavioral and bench experiments showing that moderate drinking alters protein networks associated with AD pathology, particularly of increased phosphorylated Tau. However, it is unknown whether alcohol dependence will exacerbate the effect in younger mice. The study aimed to identify the effect of alcohol dependence on early AD pathology in early middle adulthood. The experiment utilized the 3xTg mice model, which contain human genes encoding proteins involved in AD progression. Subjects underwent the vapor chamber, an established animal model of alcohol dependence, for four consecutive days for three weeks. Weekly blood alcohol content (BAC) measurements above 150 mg/dL ensured dependence. Following a 24-hour withdrawal period after the last session, tissue samples were collected from brain regions of interest. The samples were purified for RNA by affinity and absorption spectroscopy, then measured of mechanistic components (Tau, GSK-3B, CaN) by RT-PCR. There were significant differences in Tau mRNA gene fold expression in select brain regions (Prefrontal Cortex, Nuclear Accumbens, Hippocampus), but negating GSK-3B and Calcineurin changes in the Amygdala. Results suggest that alcohol dependence leads to AD-related modifications, but not by regulating amount of Tau phosphorylating components. Future experiments will observe activity of phosphorylating components to ensure mechanism.