# ApoE4 in human cortical interneuron degeneration and network activity

> **NIH NIH R21** · UNIVERSITY OF TEXAS SAN ANTONIO · 2020 · $412,125

## Abstract

PROJECT SUMMARY/ABSTRACT
Epilepsy is frequently associated with Alzheimer's Disease (AD), but whether there are shared common
mechanisms is largely unknown. Network hyperactivity due to altered functional connectivity of GABAergic
interneurons is believed to underlie many cognitive disorders and a “disease of interneurons” is the major
hypothesis for epilepsy. However, little is known about the pathophysiology of interneurons particularly in
patients with Apo4-associated AD and epilepsy. Understanding the role of ApoE4 in interneuron dysfunction
requires direct investigation of interneuron properties in human neurons derived from patients with these
mutations. Reprogramming patient somatic cells enables recapitulation of normal and pathological human
tissue developmental properties in defined conditions and a new way to identify the cellular processes
underlying complex human diseases, which can lead to mechanism-based drug discovery. Aim 1 will test
the hypothesis that ApoE4 will cause degeneration of GABAergic neurons in 3D cortical spheroids which is
associated with AD-related pathology by labeling spheroids with a Dlx1/2-GFP reporter to monitor
interneuron behavior and correlating these cellular changes with AD-related pathology. Aim 2 will test the
hypothesis that ApoE4-dependent degeneration will lead to hyperexcitability in 3D cortical spheroids by
performing multi-electrode array recordings to measure baseline neural activity and after exposure with
different anti-seizure drugs. Together, these studies are expected to provide a greater understanding of
how ApoE4 functions in human cortical interneuron development and function at the network level,
therefore contributing to the understanding of the pathophysiology of AD, which could help uncover new
strategies to treat patients with AD and epilepsy.

## Key facts

- **NIH application ID:** 9916999
- **Project number:** 1R21AG066496-01
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Jenny Hsieh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,125
- **Award type:** 1
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916999

## Citation

> US National Institutes of Health, RePORTER application 9916999, ApoE4 in human cortical interneuron degeneration and network activity (1R21AG066496-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9916999. Licensed CC0.

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