# tRNA-derived RNA Fragments (tRF) as Prognostic and Diagnostic Biomarkers for Alzheimer’s Disease

> **NIH NIH R61** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $799,998

## Abstract

PROJECT SUMMARY/ABSTRACT
tRNA-derived RNA Fragments (tRFs), a newly discovered family of non-coding RNAs (ncRNAs), are emerging
as essential disease biomarkers and regulators. Our recent publication demonstrated that tRFs are the most
impacted small ncRNAs (sncRNAs) by Alzheimer's disease (AD) in the hippocampus. The changes are mainly
from five tRFs, with one proven to correlate with the disease severity of AD experimentally. The correlation
between an AD-impacted tRF and AD severity was also present in serum samples , supporting tRFs as promising
AD indicators and potential prognostic/diagnostic biomarkers. Herein, we propose exploring a combination of an
unbiased discovery method and a newly developed biomedical quantification approach to investigate whether
the expression level of tRFs in the peripheral serum reflects the onset and progress of AD. During the discovery
R61 phase, we will determine the clinical reliability of serum biomarkers to differentiate AD subjects from healthy
individuals or individuals with non-AD dementia or non-dementia neurodegenerative diseases (Aim 1). We will
then determine the lead tRF signatures or signature compositions and investigate the correlation between their
changes with AD severity (Aim 2). The studies of the R61 phase will be mainly cross-sectional. During the R33
phase, we will investigate whether the AD biomarkers and their quantification assay can distinguish AD from its
early mild cognitive impairment (MCI) stage. We will determine biomarker changes in disease progression in
patients between baseline and subsequent follow-up patient visits. The patients who are healthy or have stable
MCI over the years will be used as controls. The culmination of these aims will benefit both prognosis and
diagnosis of AD. The feasibility of this approach is established by sample availability and our extensive research
experience in tRFs and clinical service experience in AD. The overall goal of our research is to discover AD
molecular biomarkers that could improve AD prevention and diagnosis and monitor the therapeutic efficacy in
the future.

## Key facts

- **NIH application ID:** 10808093
- **Project number:** 5R61AG075725-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Xiaoyong Bao
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $799,998
- **Award type:** 5
- **Project period:** 2023-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808093

## Citation

> US National Institutes of Health, RePORTER application 10808093, tRNA-derived RNA Fragments (tRF) as Prognostic and Diagnostic Biomarkers for Alzheimer’s Disease (5R61AG075725-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10808093. Licensed CC0.

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