# Effects of Prenatal Alcohol Exposure on Alzheimer's Disease-associated Neuropsychiatric Symptoms

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $396,250

## Abstract

PROJECT SUMMARY / ABSTRACT
Alzheimer’s disease (AD) is the most common cause of dementia, affecting 3–11% of the United States elderly.
On the other hand, the estimated incidence of prenatal alcohol exposure (PAE)-induced mental disability or
disease is 10 per 1000 live births. Although theoretically PAE-induced mental diseases are preventable, the
prevalence of PAE has been reported to be as high as 10%-16.3%. Among a broad spectrum of PAE and AD-
associated symptoms, progressive impairment of cognition has been extensively investigated. However, limited
symptomatic relief in these patients by available medications demonstrates lack of understanding of the neuronal
substrates, especially the PAE and/or AD-associated neuropsychiatric symptoms (NPSs). It is well accepted that
apathy, the top ranked NPS in both PAE and AD, arises through interactions between genetic and environmental
factors. PAE has been considered an environmental insult to the brain and AD high risk genes have been
identified as top genetic factors facilitating the onset of NPSs. Together with the increased life expectancy by 8-
10 years in the USA in the last 50 years, the evaluation of interactions between PAE history and AD high-risk
genes at the molecular, synaptic, circuit, and behavioral levels is highly urgent. Ca2+permeable(CP)-AMPARs in
the nucleus accumbens (NAc) are hypothesized as the potential substrate in mediating the synaptic loss and the
low motivation phenotype in subjects with high risk of AD and a history of PAE. In this proposal, three Specific
Aims are designed to first evaluate, and then modify, synaptic CP-AMPARs (Aim1) and excitatory synaptic
contacts (Aim 2) in the NAc, and motivation levels (Aim 3) in F344 wild type vs. transgenic AD rats at the
adolescent, early adult and middle-aged stages. Our hope is to not only fill the gap in our understanding of
neuronal mechanisms of apathy associated with AD and PAE, but also uncover novel neurobiological targets in
the clinic to treat affected patients.

## Key facts

- **NIH application ID:** 10912554
- **Project number:** 5R01AG072897-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Yao-Ying Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2020-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912554

## Citation

> US National Institutes of Health, RePORTER application 10912554, Effects of Prenatal Alcohol Exposure on Alzheimer's Disease-associated Neuropsychiatric Symptoms (5R01AG072897-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10912554. Licensed CC0.

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