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Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia

Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) are the three major neurodegenerative dementias. In this study, we provide evidence that an alteration in extracellular vesicles (EVs) release is common across the three most common neurodegenerative dementi...

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Autores principales: Longobardi, Antonio, Benussi, Luisa, Nicsanu, Roland, Bellini, Sonia, Ferrari, Clarissa, Saraceno, Claudia, Zanardini, Roberta, Catania, Marcella, Di Fede, Giuseppe, Squitti, Rosanna, Binetti, Giuliano, Ghidoni, Roberta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148014/
https://www.ncbi.nlm.nih.gov/pubmed/34046409
http://dx.doi.org/10.3389/fcell.2021.667369
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author Longobardi, Antonio
Benussi, Luisa
Nicsanu, Roland
Bellini, Sonia
Ferrari, Clarissa
Saraceno, Claudia
Zanardini, Roberta
Catania, Marcella
Di Fede, Giuseppe
Squitti, Rosanna
Binetti, Giuliano
Ghidoni, Roberta
author_facet Longobardi, Antonio
Benussi, Luisa
Nicsanu, Roland
Bellini, Sonia
Ferrari, Clarissa
Saraceno, Claudia
Zanardini, Roberta
Catania, Marcella
Di Fede, Giuseppe
Squitti, Rosanna
Binetti, Giuliano
Ghidoni, Roberta
author_sort Longobardi, Antonio
collection PubMed
description Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) are the three major neurodegenerative dementias. In this study, we provide evidence that an alteration in extracellular vesicles (EVs) release is common across the three most common neurodegenerative dementias, AD, DLB, and FTD. Specifically, we analyzed plasma EVs in three groups of patients affected by AD, DLB, and FTD, and we found a significant reduction in EVs concentration and larger EVs size in all patient groups. We then investigated whether the loss of neurotrophic factors is also a common pathogenic mechanism among FTD, DLB, and AD, and if levels of neurotrophic factors might affect EVs release. Plasma levels of progranulin and cystatin C (CysC) were partially altered; however, taking together all variables significantly associated with the diagnostic groups only EVs size and concentration were able to distinguish patients from controls. The diagnostic performance of these two EVs parameters together (ratio) was high, with a sensitivity of 83.3% and a specificity of 86.7%, able to distinguish patients from controls but not to differentiate the different forms of dementias. Among the candidate neurotrophic factors, only CysC levels were associated with EVs concentration. Our study suggests that an alteration in the intercellular communication mediated by EVs might be a common molecular pathway underlying neurodegenerative dementias. The identification of shared disease mechanisms is of pivotal importance to develop treatments to delay disease progression. To this aim, further studies investigating plasma EVs size and concentration as early biomarkers of dementia are required.
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spelling pubmed-81480142021-05-26 Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia Longobardi, Antonio Benussi, Luisa Nicsanu, Roland Bellini, Sonia Ferrari, Clarissa Saraceno, Claudia Zanardini, Roberta Catania, Marcella Di Fede, Giuseppe Squitti, Rosanna Binetti, Giuliano Ghidoni, Roberta Front Cell Dev Biol Cell and Developmental Biology Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) are the three major neurodegenerative dementias. In this study, we provide evidence that an alteration in extracellular vesicles (EVs) release is common across the three most common neurodegenerative dementias, AD, DLB, and FTD. Specifically, we analyzed plasma EVs in three groups of patients affected by AD, DLB, and FTD, and we found a significant reduction in EVs concentration and larger EVs size in all patient groups. We then investigated whether the loss of neurotrophic factors is also a common pathogenic mechanism among FTD, DLB, and AD, and if levels of neurotrophic factors might affect EVs release. Plasma levels of progranulin and cystatin C (CysC) were partially altered; however, taking together all variables significantly associated with the diagnostic groups only EVs size and concentration were able to distinguish patients from controls. The diagnostic performance of these two EVs parameters together (ratio) was high, with a sensitivity of 83.3% and a specificity of 86.7%, able to distinguish patients from controls but not to differentiate the different forms of dementias. Among the candidate neurotrophic factors, only CysC levels were associated with EVs concentration. Our study suggests that an alteration in the intercellular communication mediated by EVs might be a common molecular pathway underlying neurodegenerative dementias. The identification of shared disease mechanisms is of pivotal importance to develop treatments to delay disease progression. To this aim, further studies investigating plasma EVs size and concentration as early biomarkers of dementia are required. Frontiers Media S.A. 2021-05-11 /pmc/articles/PMC8148014/ /pubmed/34046409 http://dx.doi.org/10.3389/fcell.2021.667369 Text en Copyright © 2021 Longobardi, Benussi, Nicsanu, Bellini, Ferrari, Saraceno, Zanardini, Catania, Di Fede, Squitti, Binetti and Ghidoni. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Longobardi, Antonio
Benussi, Luisa
Nicsanu, Roland
Bellini, Sonia
Ferrari, Clarissa
Saraceno, Claudia
Zanardini, Roberta
Catania, Marcella
Di Fede, Giuseppe
Squitti, Rosanna
Binetti, Giuliano
Ghidoni, Roberta
Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
title Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
title_full Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
title_fullStr Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
title_full_unstemmed Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
title_short Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
title_sort plasma extracellular vesicle size and concentration are altered in alzheimer’s disease, dementia with lewy bodies, and frontotemporal dementia
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148014/
https://www.ncbi.nlm.nih.gov/pubmed/34046409
http://dx.doi.org/10.3389/fcell.2021.667369
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