# The role of IncRNA Neat1 in Alzheimer's disease and related memory deficits

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $657,110

## Abstract

Project Summary
We propose experiments to rigorously investigate whether lncRNAs influence gene transcription programs in the
hippocampus in response to Alzheimer’s disease (AD) pathology, and the potential of lncRNAs to be
therapeutically leveraged to promote memory resiliency in AD.
AD progression involves profound disruptions in gene transcriptional programs in the hippocampus, the brain
region necessary for learning and memory. Epigenetic interventions to enhance memory resilience in AD are
possible. However, it is not well-understood how abnormal epigenetic control of gene transcription contributes
to AD-related memory deficits. We and others have demonstrated that epigenetic chromatin remodeling
mechanisms, like posttranslational modifications of histones, DNA methylation, and non-coding RNAs are crucial
for the regulation of memory-permissive genes in the hippocampus during memory formation. Currently, a
significant gap in knowledge exists regarding the role of long non-coding RNAs (lncRNAs) in memory formation
in the healthy brain and how it is altered in AD-related memory dysfunction. Our long-term goal is to study the
role of lncRNAs in a cell-type specific manner and to identify how these powerful epigenetic regulators impact
memory formation in AD. Our pilot data demonstrate that Neat1 is overexpressed in area CA1 of the
hippocampus from the hAPP-J20 AD model. Furthermore, we demonstrate that inhibiting Neat1 expression in
area CA1 of the hippocampus of the hAPP-J20 AD model reverses memory impairments. Pilot studies also
suggest a strong relationship between histone methylation mechanisms with Neat1 overexpression in the hAPP-
J20 AD model. Based on these preliminary results, we plan to examine the effects of manipulating Neat1 in the
hippocampus and determine effects on AD-related memory decline. To gain further mechanistic insight into
Neat1 mediated gene transcription in the hippocampus of AD mouse models, we will use state-of-the-art
approaches such as single nuclei RNA isolation followed by sequencing and Chromatin Isolation by RNA
Purification to elucidate the cell-type specific epigenetic mechanisms coupled to lncRNAs in our AD animal
models. Our overarching hypothesis is that Neat1 contributes to AD-associated transcriptional changes in
hippocampal cells, hippocampal function, and vulnerability to memory dysfunction. Our Specific Aims are as
follows: Specific Aim 1: Test the hypothesis that Neat1 impacts AD pathology in the hippocampus; Specific
Aim 2: To determine the necessity of Neat1 on AD responsive gene transcription programs in the hippocampus;
Specific Aim 3: To identify the mechanisms by which Neat1 contributes to chromatin restructuring in AD; and
Specific Aim 4: To test whether hippocampal Neat1 dysregulation contributes to AD-related memory
dysfunction. Collectively, these studies will have broad implications for treatment options for AD associated
cognitive decline.

## Key facts

- **NIH application ID:** 10828890
- **Project number:** 5R01AG082089-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Farah Dominique Lubin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $657,110
- **Award type:** 5
- **Project period:** 2023-04-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828890

## Citation

> US National Institutes of Health, RePORTER application 10828890, The role of IncRNA Neat1 in Alzheimer's disease and related memory deficits (5R01AG082089-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10828890. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*