Abstract
Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer’s disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD.
Highlights
Among neurodegenerative diseases, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, accounting for around the 25–30% of all dementia cases[14]
Despite the expected differences observed between the two processing/analysis approaches, gelsolin appeared as a promising biomarker from plasma extracellular vesicles (EVs) in order to differentiate DLB from healthy controls (HCs)
Identification of EV-presence was assessed by CD9, CD63 and CD81 staining by flow cytometry (Fig. 1B) and highest mean fluorescence intensity (MFI) fractions were considered as EV-enriched and pooled in 1.5 mL
Summary
Dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, accounting for around the 25–30% of all dementia cases[14]. Many DLB patients are clinically missed or misdiagnosed as AD or PD and, lacking or even adverse response to treatment is common[18] Attempting to solve this issue, during the last decade research has been focused on finding specific biomarkers that could better characterize these heterogeneous and complex diseases[19]. In this scenario, EVs have emerged as a perfect source of specific biomarkers as their protected content could reflect the physiological and pathological state of a specific tissue, organ or cell type[20]. Additional validation using conventional ELISA techniques further confirmed this hypothesis and, interestingly, pointed to gelsolin as a putative marker to discriminate between DLB and AD patients
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