# Alcohol and the Serotonin System in the Progression of Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $375,350

## Abstract

Project Summary / Abstract
Alcohol use disorders (AUDs) are associated with neurodegeneration and cognitive dysfunction, but the impact
of alcohol use on Alzheimer's disease and related dementias (ADRD) is unknown. Our work suggests that
chronic alcohol can alter the activity of serotonin (5-HT) neurons in the DRN, which may cause disruption in
sleep homeostasis in the early stages of ADRD. Both AUD and ADRD are associated with chronic insomnia,
but to date no studies have linked alcohol-induced sleep disturbances to tau-based neuropathology in the brain.
Sleep disruption also induces microglial activation and aging, which can promote the spread of tau pathology in
the brain. In Aim 1, we will use EEG, fiber photometry, electrophysiology and DREADD-based manipulations of
neural activity in vivo in mice expressing human tau pathology (htau mice) to determine whether chronic alcohol
exacerbates sleep deficits and whether enhanced neural activity in 5-HT neurons contributes to sleep
disruptions. In Aim 2, we will examine the effect of chronic alcohol on microglia and their contribution to the
progression of tau pathology in the DRN. In Aim 3, we will determine whether chronic alcohol can facilitate the
spread of tau pathology from the DRN to other brain regions using an AAV-based strategy for expressing tau
pathology exclusively in 5-HT neurons. 3D immunolabeling and light sheet imaging using the iDISCO technique
will be used to identify areas and quantify the extent of tau spread. We will also examine whether neural activity
in 5-HT neurons and microglial activation contributes to this spread. In total, the proposed research will provide
mechanistic insight into the impact of chronic alcohol on early accumulation and spread of tau pathology in the
brain and the later development of cognitive and memory deficits.

## Key facts

- **NIH application ID:** 10132686
- **Project number:** 1R01AA028931-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Catherine Anne Marcinkiewcz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,350
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132686

## Citation

> US National Institutes of Health, RePORTER application 10132686, Alcohol and the Serotonin System in the Progression of Alzheimer's Disease (1R01AA028931-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10132686. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*