# The role of aging-associated microRNAs in Alzheimer's disease

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $393,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Mounting evidence suggests that epigenetic changes, including microRNA (miRNA) dysregulation, contribute
to aging, psychiatric disorders and neurodegenerative disorders. Although modulations of miRNA function
have generated promising clinical data for several diseases, miRNA’s roles in brain aging and Alzheimer’s
disease (AD) have not been investigated thoroughly. During AD pathogenesis, dysregulation of insulin
signaling is evident. Abnormal accumulation of Tau and amyloid beta is hypothesized to initiate a pathogenic
cascade leading to AD. Given the critical role of these protein aggregations in AD, strategies to modulate tau
and amyloid beta are actively being pursued as therapies. Toward that end, we seek to define the role of
microRNAs (miRNAs), specifically miR-17-92, in AD pathogenesis. Instead of setting up a hypothesis based on
the previously well-known proteins and concepts, we performed unbiased transcriptomics profiling experiments
and identified miR-17-92 as the most strongly dysregulated miRNAs during brain aging. Remarkably, our
finding is consistent with a recent landmark study by the NIH Common Fund’s Genotype-Tissue Expression
(GTEx) consortium’s data using 11 human brain subregions. We hypothesize that such dysregulation of miR-
17-92 expression may directly contribute to aging process. Therefore, it will be critical to understand the
functional effect of miR-17-92 decline on brain aging and try to restore its levels to ameliorate aging effect and
AD pathogenesis. Mounting studies recently suggests that miRNA dysregulation may contribute to several
neurodegenerative disorders, including AD. Interestingly, we found that miR-17-92 regulates tau
phosphorylation and APP expression level possibly by modulating insulin signaling pathway. In this application,
we propose to investigate the role of miR-17-92 in cognition and Alzheimer’s disease. We will determine how
miR-17-92 affects learning and memory and AD-related neuropathology using novel AAV Tau mouse model
and APP knock-in mouse model. Furthermore using several innovative in vivo methods, we will investigate the
mechanism underlying the role of miR-17-92 in Tau and Abeta metabolism.

## Key facts

- **NIH application ID:** 9961455
- **Project number:** 5R01AG054102-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Jungsu Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961455

## Citation

> US National Institutes of Health, RePORTER application 9961455, The role of aging-associated microRNAs in Alzheimer's disease (5R01AG054102-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961455. Licensed CC0.

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