Monday, February 2, 2026 2/2/2026

MicroRNA lipid-nanoparticle based therapy targets neuroinflammation and ApoE dysregulation in Alzheimer’s disease

Award Number: R01AG082142
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

Group Awards By:

View Award Description

MicroRNA lipid-nanoparticle based therapy targets neuroinflammation and ApoE dysregulation in Alzheimer’s disease - Project Title: MicroRNA lipid-nanoparticle based therapy targets neuroinflammation and ApoE dysregulation in Alzheimer’s disease Abstract MicroRNAs (miRNA) are small non-coding regulatory RNA that have large impacts in health and disease. While prior studies have implicated miRNA in Alzheimer’s disease and associated dementias (ADRD), they have not been used yet in a successful therapeutic strategy. We discovered that microRNA-223 (miR-223), a miRNA residing on the X-chromosome which is enriched in microglia/macrophage cells, regulates a sexually dimorphic ApoE pathway via targeting CCAAT-enhancer-binding protein beta (CEBPβ). CEBPβ is an important regulator of neuroinflammatory response and acts as a transcription factor mediating ApoE expression. Our recent data showed that deficiency of miR-223 resulted in a substantial, female-biased elevation of CEBPβ, ApoE, and a heightened inflammatory state in macrophages and in aged mouse brain following a brain injury. Thus, miR-223 appears to regulate a sexually dimorphic microglia/macrophages-dependent increase in inflammation and ApoE as brain cells become activated in parallel with age, injury, and/or Alzheimer’s disease-related pathology. We further demonstrated that miR-223 can be targeted using a novel miRNA-liposome delivery system. Based on these exciting preliminary results, the main goals of this proposal are to test the miR-223-CEBPβ pathway in regulating inflammation-triggered ApoE dysregulation in the biological context of age, sex, and Alzheimer’s disease-relevant brain injury event; and, to test the efficacy of a novel liposome-miRNA delivery method as a potential therapeutic strategy. To complete these objectives, we will 1) confirm that miR-223 directly targets the CEBPβ-ApoE pathway in myeloid cells, and test whether liposome-miR-223 delivery affects this pathway; 2) test the miR-223-CEBPβ- ApoE pathway using a brain injury mouse model and target the pathway using the liposome miRNA delivery system in a novel miR-223 knockout mouse; 3) evaluate the miR-223-CEBPβ-ApoE pathway in human cells in parallel with neuropathological changes of Alzheimer’s disease. These studies will include assessments of brain tissue from the world-class University of Kentucky Alzheimer’s Disease Center biobank. Completion of the funded studies will extend our understanding of mechanisms regulating inflammation/ApoE pathways in the context of sex, aging, and brain injury, ultimately advancing treatments for Alzheimer’s disease. Filling these knowledge gaps could have a lasting impact on public health. Moreover, our innovative miRNA-based therapeutic strategy targeting miR-223 provides a proof of efficacy for a new drug target, particularly in females, who are vulnerable for diseases associated with neuroinflammation and ApoE dysregulation, including Alzheimer’s disease and other brain injury.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $586,701 )
2026	2026	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	4	12/22/2025	NON-COMPETING CONTINUATION	$586,701
														Subtotal = $586,701

Issue Date FY: 2025 ( Subtotal = $653,652 )
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	3	12/6/2024	NON-COMPETING CONTINUATION	$600,292
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	3	9/23/2025	NON-COMPETING CONTINUATION	$53,360
														Subtotal = $653,652

Issue Date FY: 2024 ( Subtotal = $666,990 )
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	2	5/6/2024	NON-COMPETING CONTINUATION	$66,698
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	2	12/14/2023	NON-COMPETING CONTINUATION	$600,292
														Subtotal = $666,990

Issue Date FY: 2023 ( Subtotal = $654,613 )
2023	2023	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	1	4/27/2023	NEW	-$663
2023	2023	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	1	4/10/2023	NEW	$655,276
														Subtotal = $654,613

Grand Total All Awards = $2,561,956

Top

All Categories

About

Search

Reports

Data Submission

Award Information

MicroRNA lipid-nanoparticle based therapy targets neuroinflammation and ApoE dysregulation in Alzheimer’s disease

Award Number: R01AG082142

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer