# Impact of Prenatal alcohol on Alzheimer's disease related pathology and cognitive impairment

> **NIH NIH R21** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $214,074

## Abstract

Project Summary:
Persons with fetal alcohol spectrum disorders (FASD) experience life-long neurocognitive deficits as well as
social and adaptive dysfunction, but we know virtually nothing about their health as they age. We recently
reported that prenatal alcohol-exposure (PAE) resulted in long-term alteration in cranially-directed blood flow
and reduced recovery of function after an acute ischemic injury in adulthood. This suggests that PAE is an
important risk factor for cerebrovascular diseases and consequently, for dementia and Alzheimer's disease
(AD). Young PAE rats also exhibit cognitive deficits and importantly, increased depression-related behaviors
which are early predictors of AD. Therefore, in these studies, we will utilize the transgenic TgF344-AD rat
which develops AD pathology in aging, to test the hypothesis that PAE will accelerate cerebro-vascular
impairment, behavioral dysfunction and the accumulation of AD-related brain lesions, leading to premature
aging. Moreover, we will specifically test whether male and female PAE offspring differ in their accumulation
of AD-related anatomical and neurobehavioral pathology. We will implement a vapor-chamber model of
repeated PAE, to achieve consistent binge-like maternal exposure episodes, spanning the fetal neurogenic
period. PAE and control offspring will be assessed from young adults to 15 months of age, by ultrasound
imaging of cranially directed blood flow, by a panel of behavioral assays for cognitive dysfunction and
depression-like phenotypes, as well as a panel of histological assays for AD pathology.
The investigators have a history of collaboration and application of experimental rigor in their areas of
complementary expertise in models of aging and PAE, which supports the feasibility of the proposed studies.
These studies are significant because they address a critical knowledge gap about the link between early life
adversity, i.e., PAE, and the onset of AD. We expect that, if these studies do link PAE to accelerated AD
pathology, they will help redefine FASD as a disorder of premature aging and strengthen the premise for
investigating mechanisms that link PAE to aging, as well as interventions that decouple this linkage.

## Key facts

- **NIH application ID:** 10387300
- **Project number:** 1R21AA029263-01A1
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Rajesh C Miranda
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $214,074
- **Award type:** 1
- **Project period:** 2022-02-10 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387300

## Citation

> US National Institutes of Health, RePORTER application 10387300, Impact of Prenatal alcohol on Alzheimer's disease related pathology and cognitive impairment (1R21AA029263-01A1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10387300. Licensed CC0.

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