Extracellular vesicles in the study of Alzheimer's and Parkinson's diseases: Methodologies applied from cells to biofluids

Abstract

Extracellular vesicles (EVs) are gaining increased importance in fundamental research as key players in disease pathogenic mechanisms, but also in translational and clinical research due to their value in biomarker discovery, either for diagnostics and/or therapeutics. In the first research scenario, the study of EVs isolated from neuronal models mimicking neurodegenerative diseases can open new avenues to better understand the pathological mechanisms underlying these conditions or to identify novel molecular targets for diagnosis and/or therapeutics. In the second research scenario, the easy availability of EVs in body fluids and the specificity of their cargo, which can reflect the cell of origin or disease profiles, turn these into attractive diagnostic tools. EVs with exosome‐like characteristics, circulating in the bloodstream and other peripheral biofluids, constitute a non‐invasive and rapid alternative to study several conditions, including brain‐related disorders. In both cases, several EVs isolation methods are already available, but each neuronal model or biofluid presents its own challenges. Herein, a literature overview on EVs isolation methodologies from distinct neuronal models (cellular culture and brain tissue) and body fluids (serum, plasma, cerebrospinal fluid, urine and saliva) was carried out. Focus was given to approaches employed in the context of Alzheimer's and Parkinson's diseases, and the main research findings discussed. The topics here revised will facilitate the choice of EVs isolation methodologies and potentially prompt new discoveries in EVs research and in the neurodegenerative diseases field.

Bioinformatic analysis of the SPs and NFTs proteomes unravel putative biomarker candidates for Alzheimer's disease

“…In a diagnostic perspective, EVs represent a biomarker resource as these nanovesicles can cross the blood–brain barrier, protecting their cargo from degradation. EVs were shown to transport proteins linked to AD pathology, including Aβ and Tau species, but many other molecules related with events altered in AD, as inflammatory mediators and synaptic proteins, are also present [178, 179]. Hence EVs can carry disease‐specific signatures potential useful in AD diagnostics.…”

“…dation. EVs were shown to transport proteins linked to AD pathology, including Aβ and Tau species, but many other molecules related with events altered in AD, as inflammatory mediators and synaptic proteins, are also present [178,179]. Hence EVs can carry disease-specific signatures potential useful in AD diagnostics.…”

Evaluation of α‐synuclein in CNS‐originating extracellular vesicles for Parkinsonian disorders: A systematic review and meta‐analysis

“…Two independent researchers (HBT and SSA) screened all the titles, abstracts, and full manuscripts to select articles that met the eligibility criteria. By hand, we reviewed the reference lists of eligible studies, searched Google scholar for articles measuring α‐syn in CNS‐originating EVs and detailed reviews of the literature for inclusion of eligible studies 29‐35 . Any discrepancies in article selection were resolved through discussion.…”

“…By hand, we reviewed the reference lists of eligible studies, searched Google scholar for articles measuring α-syn in CNSoriginating EVs and detailed reviews of the literature for inclusion of eligible studies. [29][30][31][32][33][34][35] Any discrepancies in article selection were resolved through discussion. The complete search strategy can be found in Table S1.…”

Evaluation of α-Synuclein in CNS-originating Extracellular Vesicles for Parkinsonian Disorders: A Systematic Review and Meta-analysis.

“…Two independent researchers (HBT and SSA) screened all the titles, abstracts, and full manuscripts to select articles that met the eligibility criteria. By hand, we reviewed the reference lists of eligible studies, screened Google scholar and detailed reviews of the literature for inclusion of eligible studies (9,13,17,20,31,51,52,54). Any discrepancies in article selection were resolved through discussion.…”