# Study of Comorbid Seizures in Alzheimer's Disease

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $401,252

## Abstract

A substantial amount of clinical reports have confirmed that patients with Alzheimer’s disease are at
increased risk for developing seizures and/or epilepsy. This non-psychiatric comorbidity causes significant
burden to the patients as well as the caregivers. However, our knowledge in this area is very limited.
Understanding the mechanisms underlying Alzheimer’s disease-associated seizures may reveal novel risk
factors and provide the opportunity to develop specific anti-epileptic therapies for Alzheimer’s disease patients.
Our recent studies discovered that the activity of tumor suppressor p53 is positively correlated with neuronal
excitability in vitro and seizure susceptibility in vivo. Because we and others have observed an up-regulation of
p53 protein levels induced by amyloid beta (Aβ), we hypothesize that elevated p53 induced by Aβ contributes to
elevated neuronal excitability and seizure susceptibility in Alzheimer’s disease. In Aim 1, we propose to
determine the cellular mechanism by which p53 promotes neuronal excitability. In Aim 2, we propose to test
whether pharmacologically or genetically inhibiting p53 is able to effectively reduce neuronal excitability in the
presence of Aβ and seizure susceptibility in an Alzheimer’s disease mouse model. We expect that completion
of our project will: (1) elucidate the mechanisms by which p53 promotes excitability; (2) uncover the key molecule
(p53) that leads to elevated seizure susceptibility in Alzheimer’s disease; and (3) suggest novel therapeutic
targets and potential therapies for Alzheimer’s disease-associated seizures and epilepsy.

## Key facts

- **NIH application ID:** 10151308
- **Project number:** 1R21AG071278-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Nien-Pei Tsai
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $401,252
- **Award type:** 1
- **Project period:** 2021-03-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151308

## Citation

> US National Institutes of Health, RePORTER application 10151308, Study of Comorbid Seizures in Alzheimer's Disease (1R21AG071278-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10151308. Licensed CC0.

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