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

Giuliano Binetti¹  Roberta Ghidoni²  Luisa Benussi²  Claudia Saraceno²  Sonia Bellini²  Roberta Zanardini²  Roland Nicsanu²  Antonio Longobardi²  Rosanna Squitti²  Marcella Catania³  Giuseppe Di Fede³  Clarissa Ferrari⁴ 

[1] MAC-Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy;Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy;Neurology 5/Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy;Service of Statistics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy;

关键词: Alzheimer’s disease;    dementia with Lewy bodies;    frontotemporal dementia;    extracellular vesicles;    nanoparticle tracking analysis;    biomarkers;   

DOI  :  10.3389/fcell.2021.667369

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown