# The Role of ApoE in Injury-Induced Neurogenesis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $398,643

## Abstract

Project Summary
Following traumatic brain injury (TBI), patients often develop significant disability in cognition, communication,
and behavioral or emotional stability. Problems with memory commonly occur following TBI and underlie some
of the morbidity accompanying each of these affected areas. In addition, there is some spontaneous recovery
after brain injury that occurs largely by unknown remodeling processes. It has been known for some time that
TBI elicits increased generation of new neurons in the hippocampus; the significance of this, however, has not
been clear. We have previously demonstrated that injury-induced neurogenesis underlies at least some of the
spontaneous recovery associated with TBI. ApoE is a gene that commonly occurs in 3 different isoforms in
humans and the kind of isoform expressed is predictive of recovery following TBI. We have identified ApoE as
an important regulator of hippocampal neurogenesis. The overall goals of this project are to determine how
ApoE directs injury-induced neurogenesis following TBI and to investigate mechanisms that regulate this
process. In Specific Aim 1, we will define the ApoE-dependent memory trace after injury to get a comprehensive
picture of how altered hippocampal circuitry affects the entire brain. For Specific Aim 2, we will use our recently
generated ApoE4 mouse to conditionally replace ApoE with human ApoE4 and prove our underlying hypothesis
that ApoE4 functions as a dominant negative. Finally, in Specific Aim 3, we will elucidate the mechanism
underlying ApoE’s role in injury-induced neurogenesis by exploring how microglial TREM2 regulates this process
via binding of astrocytic ApoE. This project will therefore serve as the basis for translational studies aimed at
using the presence of specific ApoE isoforms in humans to direct reparative therapy following serious brain
injuries such as TBI.

## Key facts

- **NIH application ID:** 10875583
- **Project number:** 5R01NS095803-07
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Steven Gerard Kernie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $398,643
- **Award type:** 5
- **Project period:** 2017-01-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875583

## Citation

> US National Institutes of Health, RePORTER application 10875583, The Role of ApoE in Injury-Induced Neurogenesis (5R01NS095803-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10875583. Licensed CC0.

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