L1CAM-Enriched Extracellular Vesicle MicroRNAs in Mild Cognitive Impairment and Alzheimer’s Disease: An Exploratory Study
5 affiliations
- 1Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), Loc. Burga 44, 87050 Mangone, Italy
- 2Department of Biology, Ecology and Earth Sciences (DiBEST) University of Calabria, 87036 Rende, Italy
- 3Genomix4Life Srl, 84081 Baronissi, Italy
- 4Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), Via U. La Malfa 153, 90146 Palermo, Italy
- 5Regional Neurogenetic Centre (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, Italy
Abstract
Early diagnosis of Alzheimer’s disease (AD) and the identification of reliable molecular biomarkers remain critical clinical needs. In this context, extracellular vesicles (EVs) enriched by L1CAM immunocapture—L1CAM-enriched EVs—a fraction widely used to obtain material of putative neuronal origin, have been proposed as a minimally invasive source of information on brain molecular changes. We conducted next-generation sequencing (NGS) of microRNAs (miRNAs) from L1CAM-enriched EVs isolated from the plasma of 11 AD patients, 11 mild cognitive impairment (MCI) individuals, and 14 healthy controls (CTRs) to identify a candidate molecular signature. Our analysis identified five differentially expressed miRNAs—miR-423-5p, miR-122-5p, miR-151b, miR-16-5p, and miR-149-3p—in MCI individuals. Three of these—miR-423-5p, miR-122-5p and miR-151b—were higher in MCI and lower in AD, a pattern that differentiated the two clinically defined groups. Furthermore, enrichment analysis of the predicted targets of the differentially expressed miRNAs identified processes relevant to neurodegeneration, including synaptic organisation, cytoskeletal dynamics, and protein degradation. Overall, these preliminary findings identify blood-based L1CAM-enriched EV miRNAs as candidates for further evaluation in cognitive impairment. While validation in larger, biomarker-confirmed and independent cohorts is required, this exploratory study provides data that may guide the design of future biomarker studies.
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BibTeX
@article{benedittis2026l1camenriched,
title = {{L1CAM-Enriched Extracellular Vesicle MicroRNAs in Mild Cognitive Impairment and Alzheimer’s Disease: An Exploratory Study}},
author = {Selene De Benedittis and Patrizia Spadafora and Beatrice Maria Greco and Armando Di Palo and Olivier Gallo and Domenico Nuzzo and Pasquale Picone and Elvira Brunelli and Settimio Sesti and Alberto Montesanto and Giuseppe Passarino and Katia Risoleo and Francesca Ferrise and Rosanna Colao and Raffaele Maletta and Giovanna Marchese and Francesca Cavalcanti},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209301},
url = {https://www.mdpi.com/1422-0067/27/20/9301},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - L1CAM-Enriched Extracellular Vesicle MicroRNAs in Mild Cognitive Impairment and Alzheimer’s Disease: An Exploratory Study
AU - Selene De Benedittis
AU - Patrizia Spadafora
AU - Beatrice Maria Greco
AU - Armando Di Palo
AU - Olivier Gallo
AU - Domenico Nuzzo
AU - Pasquale Picone
AU - Elvira Brunelli
AU - Settimio Sesti
AU - Alberto Montesanto
AU - Giuseppe Passarino
AU - Katia Risoleo
AU - Francesca Ferrise
AU - Rosanna Colao
AU - Raffaele Maletta
AU - Giovanna Marchese
AU - Francesca Cavalcanti
PY - 2026
DA - 2026/10/20
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209301
UR - https://www.mdpi.com/1422-0067/27/20/9301
AB - Early diagnosis of Alzheimer’s disease (AD) and the identification of reliable molecular biomarkers remain critical clinical needs. In this context, extracellular vesicles (EVs) enriched by L1CAM immunocapture—L1CAM-enriched EVs—a fraction widely used to obtain material of putative neuronal origin, have been proposed as a minimally invasive source of information on brain molecular changes. We conducted next-generation sequencing (NGS) of microRNAs (miRNAs) from L1CAM-enriched EVs isolated from the plasma of 11 AD patients, 11 mild cognitive impairment (MCI) individuals, and 14 healthy controls (CTRs) to identify a candidate molecular signature. Our analysis identified five differentially expressed miRNAs—miR-423-5p, miR-122-5p, miR-151b, miR-16-5p, and miR-149-3p—in MCI individuals. Three of these—miR-423-5p, miR-122-5p and miR-151b—were higher in MCI and lower in AD, a pattern that differentiated the two clinically defined groups. Furthermore, enrichment analysis of the predicted targets of the differentially expressed miRNAs identified processes relevant to neurodegeneration, including synaptic organisation, cytoskeletal dynamics, and protein degradation. Overall, these preliminary findings identify blood-based L1CAM-enriched EV miRNAs as candidates for further evaluation in cognitive impairment. While validation in larger, biomarker-confirmed and independent cohorts is required, this exploratory study provides data that may guide the design of future biomarker studies.
SN - 1422-0067
ER -