# Is prenatal alcohol exposure a risk factor for the onset and progression of AD/ADRD?

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2020 · $410,000

## Abstract

ABSTRACT
 This new R01 application entitled “Is prenatal alcohol exposure a risk factor for the onset and progression of
AD/ADRD?” is submitted in response to RFA-AA-20-006 “Impact of Alcohol on the Onset and Progression of
Alzheimer's Disease and Its Related Dementias”. The overarching goal is to test the novel hypothesis that
prenatal alcohol exposure may be a risk factor for predisposing Alzheimer's disease (AD) and Alzheimer's
Disease-Related Dementia (ADRD). Indeed, the literature is replete with epidemiologic discussions of alcohol
consumption in the adult as a risk factor for AD/ADRD. However, the biological underpinnings of prenatal
alcohol exposure are distinct from those of adult alcohol consumption. To date, epidemiologic studies have not
mined the prospect that prenatal alcohol exposure may be a predisposing factor for developing AD/ADRD.
Thus, this proposal rides on the premise that, whereas preclinical and clinical studies have linked prenatal
alcohol exposure to certain neurodevelopmental brain disorders, whether or not it is a potential risk factor for
developing later-life, adult-onset cognitive disorders, notably AD/ADRD, warrants investigation. To this end, we
propose three aims, employing age-matched male and female 3xTg-AD mice and leveraging our combined
expertise in investigating the effects of prenatal alcohol exposure on corticogenesis, cortical form and function
and behavioral testing.
Aim 1: Test the hypothesis that a binge-type prenatal alcohol exposure of 3xTg-AD fetuses early in gestation
disrupts corticopetal tangential migration of primordial GABAergic interneurons and their distribution in the embryonic
medial prefrontal cortex (mPFC) and hippocampus.
Aim 2: Test the hypothesis that the aberrant tangential migration is associated later in life with a precocious
deficit in hippocampal-dependent spatial learning/memory and an exacerbated impairment in mPFC-dependent
behavioral flexibility in adult 3xTg-AD mice exposed prenatally to alcohol.
Aim 3: Test the hypothesis that the precocious deficit in spatial learning/memory and the exacerbated
impairment in behavioral flexibility in the 3xTg-AD mice with PAE are associated with (1) altered number and/or
distribution of GINs and/or (2) abnormal inhibitory GABAergic and excitatory glutamatergic neurotransmission in the
mPFC and hippocampus.
 Overall, this proposal charts an unexplored and innovative direction that carries the adverse
neurodevelopment consequences of prenatal alcohol exposure into the realm of AD/ADRD research. The
findings promise to contribute new vistas into the molecular, cellular and behavioral parallelisms between
prenatal alcohol exposure and AD/ADRD as well as their intervention and treatment.

## Key facts

- **NIH application ID:** 10153017
- **Project number:** 1R01AG072900-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Hermes H Yeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,000
- **Award type:** 1
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153017

## Citation

> US National Institutes of Health, RePORTER application 10153017, Is prenatal alcohol exposure a risk factor for the onset and progression of AD/ADRD? (1R01AG072900-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153017. Licensed CC0.

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