# Functional epitranscriptomic profiling of m6A RNA modifications in Alzheimer's Disease

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT
 N6-methyladenosine (m6A) is a post-transcriptional RNA modification. Understanding of its role in
synaptic regulation of neurons is rapidly evolving. We discovered that m6A modifications are increased in
Alzheimer’s Disease (AD), the most predominant neurodegenerative disorder marked by amyloid beta (Aβ)
accumulation, tau aggregation, and synaptic deterioration. We determined that m6A-modified RNA and tau
aggregates directly interact in AD. These data led me to hypothesize that pathological tau alters the m6A
epitranscriptome in AD, which I will begin to investigate by (aim 1) determining which m6A-modified sites
and transcripts are changed in human post-mortem AD brains. My preliminary m6A-RIP-seq studies using
human and mouse AD brains suggest that differentially methylated transcripts in AD are associated with synaptic
dysregulation. I will dissect this finding by (aim 2) determining the relative contributions of pathological Aβ
and tau in driving disease-linked changed in m6A-modified transcripts, particularly between synaptosomal
and non-synaptosomal RNA preps. To achieve these goals, I will perform a novel and robust m6A sequencing
technique that I have already optimized, termed DART-seq, on both human post-mortem AD brains and brains
from mouse models expressing pathological Aβ and tau. Next, I will apply computational pipelines to analyze the
identity and infer function of m6A-modified transcripts, cross-reference these results to public AD databases,
and investigate these results in a synaptic context.
 The fellowship training plan will extend my training to include translational application by processing
human post-mortem brain tissue, computational transcriptomics by generating RNA-seq datasets, bioinformatic
approaches by analyzing and interpreting RNA-seq datasets, data integration by cross-referencing DART-seq
results to publicly available AD datasets, subcellular fractionation by isolating synaptosomes, and scientific
communication by disseminating my results through conference presentations, seminars, and publications.
 The environment of the research training will occur at Boston University, Massachusetts, an extraordinary
institution located in one of the top global scientific hubs rich with faculty, facilities, and technologies pertaining
to the advancement of neurodegenerative breakthroughs. The research training will take place in the laboratory
of the sponsor and advisor, Dr. Benjamin Wolozin, an internationally acclaimed neuroscientist with decades of
highly impactful work investigating the molecular and cellular underpinnings of neurodegeneration.
 Broadly stated, the long-term objectives of this proposal are two-fold: 1) elucidate the key sites and
transcripts that become differentially m6A-modified in AD and in response to tau aggregation, 2) determine the
functional significance of these differential m6A-modified transcripts in synaptic expression, localization, and
translation. These objective...

## Key facts

- **NIH application ID:** 10998129
- **Project number:** 1F31AG090051-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Jenna Lynn Libera
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-19 → 2026-11-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998129

## Citation

> US National Institutes of Health, RePORTER application 10998129, Functional epitranscriptomic profiling of m6A RNA modifications in Alzheimer's Disease (1F31AG090051-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10998129. Licensed CC0.

---

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