# Role of microRNA-33 in Alzheimer's disease

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $389,738

## Abstract

PROJECT SUMMARY/ABSTRACT
Mounting evidence suggests that microRNA (miRNA) dysregulation may contribute to psychiatric disorders and
neurodegenerative disorders. Although modulations of miRNA function have generated promising clinical data
for several diseases, miRNA’s role in Alzheimer’s disease (AD) has not been investigated thoroughly.
Apolipoprotein E (ApoE) genotype is the strongest genetic risk factor for AD. In addition to ApoE isoform,
alterations in ApoE levels and lipidation status have been shown to influence Aβ aggregation. We and others
reported the critical roles of ATP-binding cassette transporter A1 (ABCA1) in regulating ApoE lipidation and Aβ
levels in the brain and its therapeutic potential. Increasing evidence suggests that neuroinflammation plays a
critical role in AD pathogenesis. Therefore, targeting inflammatory pathways is an emerging therapeutic
strategy, along with the direct targeting of ApoE/Aβ pathway, for AD therapy. Recently, we found that miR-33
gene deletion significantly increases ABCA1 levels and soluble Aβ clearance, leading to reduction of soluble
Aβ levels in the brain of APP/PS1 mouse model. We also identified that miR-33 regulates neuroinflammation
by directly targeting transforming growth factor β (TGFβ) receptor 1 (TGFβR1) gene. Here, we now seek to
define the role of miR-33 in ApoE and Amyloid β (Aβ) metabolism in mice (Aim 1) and neuroinflammation (Aim
2). In Aim 1, we will use ABCA1 knockout and ApoE knockout mice along with miR-33 knockout mouse
models. In Aim 2, we will use TGFβR1 knockout mouse model. Importantly, we demonstrated that antisense
oligonucleotide (ASO)-based pharmacological inhibition of miR-33 efficiently increases ABCA1 levels and
reduces soluble Aβ levels in the brain. In Aim 3, we will assess the effect of long-term treatment of anti-miR-33
ASO on Aβ deposition, neuroinflammation, and behavior in mice. We will assess the preventive and
therapeutic effect by treating anti-miR-33 ASO before and after the development of Aβ plaques and memory
deficits in APP/PS1 mice.

## Key facts

- **NIH application ID:** 9965698
- **Project number:** 5R01AG053500-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Jungsu Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,738
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965698

## Citation

> US National Institutes of Health, RePORTER application 9965698, Role of microRNA-33 in Alzheimer's disease (5R01AG053500-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9965698. Licensed CC0.

---

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