Comparison of neuron-derived extracellular vesicles miRNA profile between patients with behavioural variant frontotemporal dementia and primary psychiatric disorders.

Authors

Giulia Giudici, Chiara Fenoglio, Maria Serpente, Andrea Arighi, Marina Arcaro, Giuseppe Delvecchio, Paolo Brambilla, Luca Sacchi, Manuela Pintus, Vittoria Borracci, Sterre C M De Boer, Ramon Landin-Romero, Olivier Piguet, Ishana Rue, Lina Riedl, Janine Diehl-Schmid, Simon Ducharme, Glenda Halliday, Yolande A L Pijnenburg, Daniela Galimberti

Published in

Neurobiology of disease. Pages 107132. Oct 02, 2025. Epub Oct 02, 2025.

Abstract

The behavioural variant of frontotemporal dementia (bvFTD) often overlaps clinically with primary psychiatric disorders (PPD), leading to frequent misdiagnosis and delayed intervention. The "Diagnostic and Prognostic Precision Algorithm for behavioural variant Frontotemporal Dementia" (DIPPA-FTD) study aims to enhance bvFTD diagnosis by integrating clinical and molecular biomarkers. Among these, neuron-derived extracellular vesicles (NDEVs) isolated from plasma offer a minimally invasive means to investigate central nervous system alterations through microRNA (miRNA) profiling. This study analyzed miRNAs expression in NDEVs from patients with bvFTD, PPD, and healthy controls. In a retrospective cohort of 80 participants, six miRNAs differentiated bvFTD from PPD; however, these findings were not replicated in a prospective cohort comprised of 86 participants, suggesting heterogeneity within PPD. Further analysis identified three miRNAs (hsa-miR-106b-5p, hsa-miR-126-3p, and hsa-miR-342-3p) that significantly distinguished bvFTD from a sub-group of PPD, namely bipolar disorder (BD). The downregulation of hsa-miR-106b-5p and hsa-miR-126-3p, implicated in neuroprotection and vascular integrity, contrasted with the upregulation of hsa-miR-342-3p, which is associated with neuroinflammation. Bioinformatics analysis revealed E2F1, a transcription factor linked to autophagy and neuronal apoptosis, as a common target of significantly de-regulated miRNAs, further highlighting their potential pathophysiological role. These findings suggest that miRNAs signatures in NDEVs may serve as valuable biomarkers to differentiate bvFTD from BD, although further validation is required.

PMID:
41046106
Bibliographic data and abstract were imported from PubMed on 05 Oct 2025.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.