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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.667369/full |
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| author | Antonio Longobardi Luisa Benussi Roland Nicsanu Sonia Bellini Clarissa Ferrari Claudia Saraceno Roberta Zanardini Marcella Catania Giuseppe Di Fede Rosanna Squitti Giuliano Binetti Giuliano Binetti Roberta Ghidoni |
| author_facet | Antonio Longobardi Luisa Benussi Roland Nicsanu Sonia Bellini Clarissa Ferrari Claudia Saraceno Roberta Zanardini Marcella Catania Giuseppe Di Fede Rosanna Squitti Giuliano Binetti Giuliano Binetti Roberta Ghidoni |
| author_sort | Antonio Longobardi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T18:56:02Z |
| format | Article |
| id | doaj.art-c67abb90d12c461887e0d76b551c50b0 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T18:56:02Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c67abb90d12c461887e0d76b551c50b02022-12-21T22:20:31ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-05-01910.3389/fcell.2021.667369667369Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal DementiaAntonio Longobardi0Luisa Benussi1Roland Nicsanu2Sonia Bellini3Clarissa Ferrari4Claudia Saraceno5Roberta Zanardini6Marcella Catania7Giuseppe Di Fede8Rosanna Squitti9Giuliano Binetti10Giuliano Binetti11Roberta Ghidoni12Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyService of Statistics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyNeurology 5/Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, ItalyNeurology 5/Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMAC-Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, ItalyAlzheimer’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.https://www.frontiersin.org/articles/10.3389/fcell.2021.667369/fullAlzheimer’s diseasedementia with Lewy bodiesfrontotemporal dementiaextracellular vesiclesnanoparticle tracking analysisbiomarkers |
| spellingShingle | Antonio Longobardi Luisa Benussi Roland Nicsanu Sonia Bellini Clarissa Ferrari Claudia Saraceno Roberta Zanardini Marcella Catania Giuseppe Di Fede Rosanna Squitti Giuliano Binetti Giuliano Binetti Roberta Ghidoni Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia Frontiers in Cell and Developmental Biology Alzheimer’s disease dementia with Lewy bodies frontotemporal dementia extracellular vesicles nanoparticle tracking analysis biomarkers |
| 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 | Alzheimer’s disease dementia with Lewy bodies frontotemporal dementia extracellular vesicles nanoparticle tracking analysis biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.667369/full |
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