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Differential miRNA expression in neural-enriched extracellular vesicles as potential biomarker for frontotemporal dementia and bipolar disorder
María Serpente, Giuseppe Delvecchio, Chiara Fenoglio, Lorena Di Consoli, Giovanni De Giudici, Vittoria Borracci, Emanuela Rotondo, Marina Arcaro et al.. Neurobiology of Disease, 2025-03-08
Topic: Brain proteins, microglia and lab models
Behavioral variant of Frontotemporal Dementia (bvFTD) and Bipolar Disorder (BD) share overlapping symptoms, complicating diagnosis. BvFTD, especially linked to C9orf72 expansions, often mimics BD, highlighting the need for reliable biomarkers. This study aimed to differentiate bvFTD from BD using miRNA profiles in neural-enriched extracellular vesicles (NEVs). A cohort of 100 subjects was analyzed: 40 bvFTD (20 sporadic, 20 C9orf72 carriers), 40 BD, and 20 healthy controls. NEVs were isolated from plasma and profiled using real-time PCR. Among 754 miRNAs, 11 were significantly deregulated in bvFTD and BD. MiR-152-5p was downregulated in sporadic bvFTD, while let-7b, let-7e, miR-18b, and miR-142-5p were altered in C9orf72 carriers. BD patients showed distinct patterns in miR-331-5p, miR-335, and miR-345 compared to bvFTD. Bioinformatics analyses revealed that let-7e, let-7b, miR-18b, and miR-142-5p share common long non-coding RNA (lncRNA) targets, including XIST, NEAT1, and OIP5-AS1, suggesting their involvement in molecular networks relevant to C9orf72-related bvFTD. These miRNA signatures can differentiate bvFTD from BD, especially in C9orf72-related cases, and offer insights into disease pathways. Further research is needed to validate these findings and explore their clinical application. • Novel miRNAs deregulated in NEVs of bvFTD and BD patients identified. • Differential expression profiles of miRNAs observed in C9orf72 expansion carriers. • Bioinformatic analysis identified putative lncRNA targets (XIST, NEAT1, OIP5-AS1, KCNQ1OT1), which require further validation. • miR-152-5p linked to vesicular transport and cellular degradation processes. • miR-331-5p, miR-335, and miR-345 target key pathways in immune and cell cycle regulation.
Key findings
- Among 754 miRNAs, 11 were significantly deregulated in bvFTD and BD.
- BD patients showed distinct patterns in miR-331-5p, miR-335, and miR-345 compared to bvFTD.
- Bioinformatics analyses revealed that let-7e, let-7b, miR-18b, and miR-142-5p share common long non-coding RNA (lncRNA) targets, including XIST, NEAT1, and OIP5-AS1, suggesting their involvement in molecular networks relevant to C9orf72-related bvFTD.
- Further research is needed to validate these findings and explore their clinical application. • Novel miRNAs deregulated in NEVs of bvFTD and BD patients identified. • Differential expression profiles of miRNAs observed in C9orf72 expansion carriers. • Bioinformatic analysis identified putative lncRNA targets (XIST, NEAT1, OIP5-AS1, KCNQ1OT1), which require further validation. • miR-152-5p linked to vesicular transport and cellular degradation processes. • miR-331-5p, miR-335, and miR-345 target key pathways in immune and cell cycle regulation.
Why it matters
This study found that miRNA signatures in neural-enriched extracellular vesicles can differentiate behavioral variant frontotemporal dementia from bipolar disorder, especially in C9orf72-related cases. The authors state that further research is needed to validate these findings and explore their clinical application, so this is not yet a treatment or cure.
Study details
- Participants100
- Evidence strengthModerate
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of Disease) |
| Journal's citation record | 2 / 4 | Neurobiology of Disease: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 100 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Daniela Galimberti: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Milan: institution h-index 1,023 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40064379) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.nbd.2025.106867
- PubMed: 40064379
- Original source →
- Free full text: Neurobiology of Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Serpente, M., Delvecchio, G., Fenoglio, C., Di Consoli, L., De Giudici, G., Borracci, V., et al. (2025). Differential miRNA expression in neural-enriched extracellular vesicles as potential biomarker for frontotemporal dementia and bipolar disorder. Neurobiology of Disease. https://doi.org/10.1016/j.nbd.2025.106867
Vancouver
Serpente M, Delvecchio G, Fenoglio C, Di Consoli L, De Giudici G, Borracci V, et al. Differential miRNA expression in neural-enriched extracellular vesicles as potential biomarker for frontotemporal dementia and bipolar disorder. Neurobiology of Disease. 2025. doi:10.1016/j.nbd.2025.106867. PMID: 40064379.
BibTeX
@article{serpente2025-40064379,
author = {Serpente, María and Delvecchio, Giuseppe and Fenoglio, Chiara and Di Consoli, Lorena and De Giudici, Giovanni and Borracci, Vittoria and Rotondo, Emanuela and Arcaro, Marina and others},
title = {{Differential miRNA expression in neural-enriched extracellular vesicles as potential biomarker for frontotemporal dementia and bipolar disorder}},
journal = {Neurobiology of Disease},
year = {2025},
doi = {10.1016/j.nbd.2025.106867},
pmid = {40064379},
url = {https://doi.org/10.1016/j.nbd.2025.106867}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.