Blood–CSF MiRNA Signatures in Alzheimer’s Disease Reveal Novel Biomarker Candidates: A Systematic Review
4 affiliations
- 1Molecular Studies Applied to Health Sciences Group (EMAS), Department of Medical Sciences, Faculty of Medicine of Ciudad Real, Institute of Biomedicine (IB-UCLM), University of Castilla-La Mancha, Paseo de Moledores s/n, 13071 Ciudad Real, Spain
- 2Multidisciplinary Group in Psychiatry and Translational Neuroscience, Health Research Institute of Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- 3Department of Neurology, General University Hospital of Albacete, 02008 Albacete, Spain
- 4Research Group on Cerebrovascular, Neurodegenerative and Neuro-Oncological Diseases, Health Research Institute of Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. MicroRNAs (miRNAs) have emerged as promising regulators of AD-related pathways and potential minimally invasive biomarkers. However, existing meta-analyses have yielded inconsistent results, and whether miRNA signatures are conserved across biological fluids remains unclear. The present work aimed to systematically review studies performing miRNA discovery or multi-candidate profiling in blood and CSF during the last 15 years, in order to identify miRNAs showing significant and consistent differential expression across independent studies. By systematically comparing the direction and consistency of miRNA dysregulation across independent studies and biological sources, we identified 80 miRNAs consistently dysregulated in both blood and CSF, revealing a reproducible cross-fluid signature of AD-associated molecular alterations. Notably, miR-451a and miR-16-5p emerged among the most consistently dysregulated miRNAs across fluids. In contrast, several miRNAs displayed divergent or compartment-specific patterns, highlighting that blood and CSF may capture distinct aspects of AD-related molecular changes. Among these, miR-484, miR-3200-3p and miR-598 were identified as novel CSF candidates, while miR-20a-5p, miR-363-3p and miR-5006-3p represented novel blood-specific candidates. Furthermore, a substantial proportion of detected miRNAs was associated with extracellular vesicle/exosomal fractions, supporting their potential stability and biological relevance. Overall, our findings demonstrate that AD-associated miRNA dysregulation comprises both conserved and biofluid-specific signatures. From a clinical perspective, the current evidence primarily supports further evaluation of miRNAs as diagnostic/discriminative biomarkers rather than validated tools for early detection, disease monitoring, or prognosis. Their clinical translation remains limited by biofluid and methodological heterogeneity and requires harmonized cross-cohort and longitudinal validation.
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BibTeX
@article{benchohra2026bloodcsf,
title = {{Blood–CSF MiRNA Signatures in Alzheimer’s Disease Reveal Novel Biomarker Candidates: A Systematic Review}},
author = {Asmae Benchohra and Cristina Juárez-Alía and Gemma Serrano and Tomás Segura and Juan R. Peinado and Yoana Rabanal-Ruiz},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219506},
url = {https://www.mdpi.com/1422-0067/27/21/9506},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Blood–CSF MiRNA Signatures in Alzheimer’s Disease Reveal Novel Biomarker Candidates: A Systematic Review
AU - Asmae Benchohra
AU - Cristina Juárez-Alía
AU - Gemma Serrano
AU - Tomás Segura
AU - Juan R. Peinado
AU - Yoana Rabanal-Ruiz
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219506
UR - https://www.mdpi.com/1422-0067/27/21/9506
AB - Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. MicroRNAs (miRNAs) have emerged as promising regulators of AD-related pathways and potential minimally invasive biomarkers. However, existing meta-analyses have yielded inconsistent results, and whether miRNA signatures are conserved across biological fluids remains unclear. The present work aimed to systematically review studies performing miRNA discovery or multi-candidate profiling in blood and CSF during the last 15 years, in order to identify miRNAs showing significant and consistent differential expression across independent studies. By systematically comparing the direction and consistency of miRNA dysregulation across independent studies and biological sources, we identified 80 miRNAs consistently dysregulated in both blood and CSF, revealing a reproducible cross-fluid signature of AD-associated molecular alterations. Notably, miR-451a and miR-16-5p emerged among the most consistently dysregulated miRNAs across fluids. In contrast, several miRNAs displayed divergent or compartment-specific patterns, highlighting that blood and CSF may capture distinct aspects of AD-related molecular changes. Among these, miR-484, miR-3200-3p and miR-598 were identified as novel CSF candidates, while miR-20a-5p, miR-363-3p and miR-5006-3p represented novel blood-specific candidates. Furthermore, a substantial proportion of detected miRNAs was associated with extracellular vesicle/exosomal fractions, supporting their potential stability and biological relevance. Overall, our findings demonstrate that AD-associated miRNA dysregulation comprises both conserved and biofluid-specific signatures. From a clinical perspective, the current evidence primarily supports further evaluation of miRNAs as diagnostic/discriminative biomarkers rather than validated tools for early detection, disease monitoring, or prognosis. Their clinical translation remains limited by biofluid and methodological heterogeneity and requires harmonized cross-cohort and longitudinal validation.
SN - 1422-0067
ER -