# Plasticity circuits in Alzheimer s disease

> **NIH NIH RF1** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $155,000

## Abstract

Project Summary/ Abstract
The mechanism underlying progressive memory loss and cognitive deterioration in Alzheimer’s disease (AD)
is not fully understood and effective approaches to prevent or reverse memory deficits are unavailable. Here
we show that augmentation of hippocampal neurogenesis in a mouse model of familial Alzheimer’s disease
(FAD) reverses deficits in spatial recognition. Notably, new neurons are recruited into the memory circuit and
serve as part of the engram during memory acquisition and retrieval. The number of new neurons in the
engram of FAD mice is reduced compared to wild type. However, it is significantly increased following
augmentation of neurogenesis. Importantly, new neurons encompass the majority of engram cells during
memory retrieval. Thus, this project will test the hypothesis that new neurons play a major role in the engram and
that increasing hippocampal neurogenesis in FAD restores the engram and rescues learning and memory. By
manipulating levels of neurogenesis in FAD mouse models and using engram labeling techniques,
experiments in Aim 1 will establish the role of new hippocampal neurons in the engram in FAD. Experiments
in Aim 2 will determine the role of neurogenesis in memory retrieval in FAD. Aim 3 will unravel the signaling
pathways underlying impaired hippocampal neurogenesis and engram function in AD. Aim 4 will examine
the association between Alzheimer’s pathological hallmarks and the Engram. This program is designed to
establish the role of hippocampal neurogenesis in cognitive deficits in AD and determine the efficacy of
augmented neurogenesis in rescuing learning and memory in this disorder.

## Key facts

- **NIH application ID:** 10409892
- **Project number:** 3RF1AG033570-11S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Orly Lazarov
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,000
- **Award type:** 3
- **Project period:** 2009-03-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409892

## Citation

> US National Institutes of Health, RePORTER application 10409892, Plasticity circuits in Alzheimer s disease (3RF1AG033570-11S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10409892. Licensed CC0.

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