miR-423-5p and miR-92a-3p in Alzheimer's disease: relationship with pathology and cognition.
| Title: | miR-423-5p and miR-92a-3p in Alzheimer's disease: relationship with pathology and cognition. |
|---|---|
| Authors: | Han SW; Department of Neurology, Soonchunhyang University Seoul Hospital and Soonchunhyang University College of Medicine, Seoul, Republic of Korea.; Park YH; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea.; Pyun JM; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea.; Bice PJ; Department of Radiology and Imaging Sciences, Center for Computational Biology and Bioinformatics, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, United States.; Kim S; Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Republic of Korea.; Saykin AJ; Department of Radiology and Imaging Sciences, Center for Computational Biology and Bioinformatics, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, United States.; Nho K; Department of Radiology and Imaging Sciences, Center for Computational Biology and Bioinformatics, Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, United States. |
| Source: | Frontiers in aging neuroscience [Front Aging Neurosci] 2025 Jul 22; Vol. 17, pp. 1637368. Date of Electronic Publication: 2025 Jul 22 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101525824 Publication Model: eCollection Cited Medium: Print ISSN: 1663-4365 (Print) Linking ISSN: 16634365 NLM ISO Abbreviation: Front Aging Neurosci Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Lausanne : Frontiers Research Foundation |
| Abstract: | Background: MicroRNAs (miRNAs), small and highly conserved non-coding RNA molecules, have emerged as promising molecular biomarkers due to their regulatory roles in gene expression and stability in blood.; Methods: We used measurements of 64 plasma miRNAs from 145 participants in the Alzheimer's disease Neuroimaging Initiative cohort, including 74 probable AD patients and 71 cognitively normal (CN) older adults. We performed principal component analysis (PCA) with factor rotation for dimension reduction to identify AD-associated principal components (PCs) and their key miRNAs with factor loadings higher than 0.8. We investigated their association with amyloid/tau/neurodegeneration (A/T/N) biomarkers and cognition. After identifying the candidate target genes of key miRNAs, we performed pathway enrichment analysis. We conducted mediation analyses to assess the effect of the associations between miRNAs and A/T/N biomarkers on AD diagnosis and cognition. Finally, we used a machine learning approach to evaluate the performance of key miRNAs for AD classification.; Results: PCA identified one PC as significantly associated with AD. The PC was also significantly associated with CSF p-tau levels, hippocampal volume, and cognition. Two key miRNAs (miR-423-5p and miR-92a-3p) in the PC were associated with AD. Lower levels of miR-423-5p and miR-92a-3p were associated with reduced hippocampal volume and worse cognition, and lower levels of miR-423-5p were associated with higher brain amyloid deposition. Pathway enrichment analysis identified several significant biological processes, including memory, protein phosphorylation, and the phosphatidylinositol-3-phosphate biosynthetic process. Mediation analysis revealed that miR-423-5p, but not miR-92a-3p, had indirect effects on AD diagnosis and memory performance through brain amyloid deposition and brain atrophy. Machine learning analysis demonstrated that incorporating two key miRNAs improved the performance of demographic information for AD classification.; Conclusion: Plasma miR-423-5p and miR-92a-3p are implicated in AD pathology and cognitive decline, providing insights into their roles in disease mechanisms. This study suggests the potential of these miRNAs as blood-based molecular biomarkers for AD.; (Copyright © 2025 Han, Park, Pyun, Bice, Kim, Saykin and Nho.) |
| Competing Interests: | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor AT declared a past collaboration with the authors PB, AS and KN. |
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| Grant Information: | R56 AG051086 United States AG NIA NIH HHS; U19 AG024904 United States AG NIA NIH HHS; P30 AG072976 United States AG NIA NIH HHS; RF1 AG078299 United States AG NIA NIH HHS; R01 AG084624 United States AG NIA NIH HHS; U01 AG072177 United States AG NIA NIH HHS; U19 AG074879 United States AG NIA NIH HHS; U01 AG024904 United States AG NIA NIH HHS |
| Contributed Indexing: | Keywords: Alzheimer’s disease; MicroRNAs; cognitive decline; machine learning; miR-423-5p; miR-92a-3p |
| Entry Date(s): | Date Created: 20250806 Latest Revision: 20260517 |
| Update Code: | 20260517 |
| PubMed Central ID: | PMC12321855 |
| DOI: | 10.3389/fnagi.2025.1637368 |
| PMID: | 40766177 |
| Database: | MEDLINE |
Journal Article