Author:
Cano Amanda,Esteban-de-Antonio Ester,Bernuz Mireia,Puerta Raquel,García-González Pablo,de Rojas Itziar,Olivé Claudia,Pérez-Cordón Alba,Montrreal Laura,Núñez-Llaves Raúl,Sotolongo-Grau Óscar,Alarcón-Martín Emilio,Valero Sergi,Alegret Montserrat,Martín Elvira,Martino-Adami Pamela V.,Ettcheto Miren,Camins Antonio,Vivas Assumpta,Gomez-Chiari Marta,Tejero Miguel Ángel,Orellana Adelina,Tárraga Lluís,Marquié Marta,Ramírez Alfredo,Martí Mercè,Pividori María Isabel,Boada Mercè,Ruíz Agustín
Abstract
AbstractIn the clinical course of Alzheimer’s disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink© proteomics. The obtained results showed that proteins measured in pEVs from EOMCI patients with established amyloidosis correlated with CSF p-tau181 levels, brain ventricle volume changes, brain hyperintensities, and MMSE scores. In addition, the correlations of pEVs proteins with different parameters distinguished between EOMCI Aβ( +) and Aβ(-) patients, whereas the CSF or plasma proteome did not. In conclusion, our findings suggest that pEVs may be able to provide information regarding the initial amyloidotic changes of AD. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development.
Graphical Abstract
Funder
Ministerio de Ciencia e Innovación
Instituto de Salud Carlos III
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
EU Joint Programme – Neurodegenerative Disease Research
Agency for Innovation and Entrepreneurship
Innovative Medicines Initiative
Deutsche Forschungsgemeinschaft
“la Caixa” Foundation
Grifols
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
Cited by
2 articles.
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