The impact of alcohol use on health and well-being in older adults is not fully understood. Evidence suggests that alcohol abuse during mid-life exacerbates age-related cognitive decline and may increase the risk of developing dementia after age 65. Alzheimer’s disease (AD) is a major cause of dementia in older individuals but it is unclear if alcohol targets AD-linked molecular mechanisms to produce neural and behavioral pathology. This chapter is divided into two overall sections. First, we briefly review evidence suggesting that alcohol abuse promotes cognitive decline and dementia in older adults and present a re-analysis of our prior preclinical studies that assessed the impact of nondependent alcohol drinking on the neuroproteome. These data show that three primary neural mechanisms of AD (Tau, amyloid precursor protein, and presenilin-1) are the statistically most likely regulators of alcohol-sensitive protein networks in the frontal cortex and amygdala of mice, which suggests that alcohol use may promote vulnerability to AD-like pathology. Second, we present results from original preclinical studies designed to evaluate the impact of nondependent alcohol drinking on AD-like neural and behavioral pathology using
