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MicroRNA-223 Enhances Microglia-Dependent Clearance of Amyloid Beta Plaques and Ameliorates Behavioral Deficits in a Mouse Model of Alzheimer’s Disease
Krunic A, Umesh Ganesh N, Coskun U, Brennan W, Patel C, Joshi O, Lee J, Gu TS et al.. bioRxiv, 2026-07-23
Topic: Inflammation, microglia and astrocytes
Plain-language summary
The Alzheimer’s disease (AD) brain is characterized by dysregulated expression of multiple microRNAs (miRNA), positioning them as promising diagnostic and therapeutic targets. The levels of glia-enriched miR-223 are abnormal in the brains and plasma of AD patients and miR-223 is neuroprotective in models of stroke. However, whether miR-223 can be beneficial in AD is not known. Here, we report that intracerebroventricular (ICV) injection of miR-223 oligonucleotide mimic alleviated cognitive impairment, reduced amyloid beta (Aβ) pathology, and ameliorated the defects in synaptic marker expression in App NL-G-F AD model mice. Mechanistically, miR-223 induced microglial clustering around Aβ plaques with a concomitant upregulation of microglial phagocytic receptors AXL, TREM2 and CD11c, while pharmacological microglial depletion abolished the plaque-clearance phenotype. Moreover, in human iPSC-derived microglia miR-223 directly targeted multiple genes in the endo-lysosomal pathway, including AD risk gene SPPL2A , indicating that it acts as a major regulator of microglial phenotype. Lastly, long-term AAV-mediated overexpression of miR-223 recapitulates its beneficial effects on cognition, pathology, and synaptic marker expression. Our study demonstrates a novel approach for the treatment of AD using miR-223 and highlights the potential of RNAi-based therapeutics in neurodegenerative disease.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Krunic, A., Umesh Ganesh, N., Coskun, U., Brennan, W., Patel, C., Joshi, O., et al. (2026). MicroRNA-223 Enhances Microglia-Dependent Clearance of Amyloid Beta Plaques and Ameliorates Behavioral Deficits in a Mouse Model of Alzheimer’s Disease. bioRxiv. https://doi.org/10.64898/2026.07.20.738977
Vancouver
Krunic A, Umesh Ganesh N, Coskun U, Brennan W, Patel C, Joshi O, et al. MicroRNA-223 Enhances Microglia-Dependent Clearance of Amyloid Beta Plaques and Ameliorates Behavioral Deficits in a Mouse Model of Alzheimer’s Disease. bioRxiv. 2026. doi:10.64898/2026.07.20.738977.
BibTeX
@article{krunic2026-ec5a997c,
author = {Krunic, A. and Umesh Ganesh, N. and Coskun, U. and Brennan, W. and Patel, C. and Joshi, O. and Lee, J. and Gu, T. S. and others},
title = {{MicroRNA-223 Enhances Microglia-Dependent Clearance of Amyloid Beta Plaques and Ameliorates Behavioral Deficits in a Mouse Model of Alzheimer’s Disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.07.20.738977},
url = {https://doi.org/10.64898/2026.07.20.738977}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Here, we report that intracerebroventricular (ICV) injection of miR-223 oligonucleotide mimic alleviated cognitive impairment, reduced amyloid beta (Aβ) pathology, and ameliorated the defects in synaptic marker expression in App NL-G-F AD model mice.
- Mechanistically, miR-223 induced microglial clustering around Aβ plaques with a concomitant upregulation of microglial phagocytic receptors AXL, TREM2 and CD11c, while pharmacological microglial depletion abolished the plaque-clearance phenotype.
- Moreover, in human iPSC-derived microglia miR-223 directly targeted multiple genes in the endo-lysosomal pathway, including AD risk gene SPPL2A , indicating that it acts as a major regulator of microglial phenotype.
- Lastly, long-term AAV-mediated overexpression of miR-223 recapitulates its beneficial effects on cognition, pathology, and synaptic marker expression.
- Our study demonstrates a novel approach for the treatment of AD using miR-223 and highlights the potential of RNAi-based therapeutics in neurodegenerative disease.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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