# Wake Forest Translational Alcohol Research Center

> **NIH NIH P50** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $384,750

## Abstract

PROJECT SUMMARY
As the most common form of dementia, Alzheimer’s disease (AD) is a neurodegenerative disorder that affects
approximately 30 million people worldwide. AD is characterized by the aggregation of extracellular amyloid β
(Aβ) into amyloid plaques and intracellular tau into neurofibrillary tangles (NFTs), both of which begin to
accumulate ~15 years before cognitive decline. Alcohol is among the most widely abused drugs in the world
and problems arising from alcohol use disorder (AUD) represent a major public health concern.
Epidemiological studies consistently identify AUD as a significant and independent predictor of AD in older
adults. Heavy drinking in AD patients is associated with faster cognitive decline, suggesting that alcohol
consumption may contribute to AD progression. However, it is unknown how alcohol intake during the pre-
symptomatic period drives the AD pathogenesis, specifically, the production, clearance, and aggregation of Aβ
and tau, the two pathological hallmarks of AD. In humans, monkeys, and rodents, the hippocampus is a brain
area critical for memory formation and encoding and is especially vulnerable to the neurodegenerative
processes and cognitive impairments associated with AD. The hippocampus is also compromised in AUD, with
multiple lines of evidence suggesting that maladaptive changes in hippocampus-containing brain circuits leads
to increases in fear- and anxiety-like behaviors and decreases in cognitive performance. Despite the
availability of rodent models for alcohol dependence and mouse models for AD, very few studies have
investigated the effects of alcohol exposure in AD mouse models. The central hypothesis of this proposal is
that aberrant hippocampal excitatory synaptic function arising from ethanol exposure promotes the
onset and progression of neuropathology and impairments in behavior and synaptic plasticity
associated with AD. Toward this end, the work described in this proposal capitalizes on the research
strengths of investigators in the Wake Forest Translational Alcohol Research Center and the Wake Forest
Alzheimer’s Disease Research Center. We will combine a well-established model of ethanol dependence and
a widely used AD mouse model to elucidate the interaction between AUD and AD at the molecular, behavioral,
and synaptic levels. In addition, we will take advantage of an established cohort of monkeys undergoing a
longitudinal study of ethanol consumption to determine if AD biomarkers correlate with ethanol intake.
Collectively, these experiments will provide critically needed insight into the relationship of AUD and AD at the
molecular, cellular, circuit, and whole-brain levels across animal models (rodents and non-human primates)
and human subjects.

## Key facts

- **NIH application ID:** 10123149
- **Project number:** 3P50AA026117-03S1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jeffrey L. Weiner
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,750
- **Award type:** 3
- **Project period:** 2017-12-10 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123149

## Citation

> US National Institutes of Health, RePORTER application 10123149, Wake Forest Translational Alcohol Research Center (3P50AA026117-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123149. Licensed CC0.

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