Elsevier

Neurobiology of Aging

Volume 74, February 2019, Pages 15-20
Neurobiology of Aging

Review
Extracellular vesicles, new actors in the search for biomarkers of dementias

https://doi.org/10.1016/j.neurobiolaging.2018.10.006Get rights and content

Highlights

  • Specific biomarkers will help to solve overlapping features of different dementias.

  • Extracellular vesicles (EVs) are a reliable and stable biomarker source, accessible in several body fluids.

  • EV proteins and miRNAs could define the specific biosignature of the pathology.

  • EVs may contain potential biomarkers.

  • Efforts in the standardization and consensus of EV-related techniques are required.

Abstract

Increased life expectancy impacts directly on the number of older people worldwide with the associated increase in neurodegenerative diseases. Besides their social implications, the different forms of dementia, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies or frontotemporal dementia, show clinical and pathological overlaps; this hinders their specific and differential diagnosis. To date, biomarkers for each of these types of dementia have been investigated in the cerebrospinal fluid or blood. More recently, the field of biomarker search found a new opportunity to improve diagnosis in extracellular vesicles (EVs). EVs are released by cells including those of the central nervous system and these can be isolated from cerebrospinal fluid and blood. This review summarizes the current knowledge related to the search for dementia biomarkers in the field of EVs including studies of specific EV content, mainly proteins such as α-synuclein or tau and RNA species.

Introduction

Life expectancy has significantly increased during the last decades, so that around 900 million people are aged over 60 years (Global burden of Disease Study Collaborators, 2015), raising the possibility of developing aging-related chronic diseases (Prince et al., 2016). In this aging context, neurodegenerative diseases (NDDs) and dementia-related disorders are one of the most critical public health problems in our society. The term dementia generally refers to a group of pathological situations presenting symptoms characterized by the loss of memory and other intellectual abilities such as decision making, problem solving, creative and critical thinking, and later also activities of daily living (Harada et al., 2013, Martin, 1999, Prizer and Zimmerman, 2018). The most studied dementia-related diseases include NDDs like Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) (http://www.alzcare.org/dementia). With the aim of disentangling the clinical and pathological overlaps between these diseases, efforts have been focused on the search of specific biomarkers for each of the disorders (Ahmed et al., 2014, Biomarkers Definitions Working Group, 2001). Therefore, this review focuses on liquid biopsy biomarkers, specifically on extracellular vesicles (EVs) as biomarker source for the differential diagnosis of dementia-related disorders.

Section snippets

Biomarkers for dementia-related disorders

AD accounts for more than 60% of all dementia cases and neuropathologically, it is characterized by the presence of neurofibrillary tangles and senile plaques (Martin, 1999, Winblad et al., 2016). The beta amyloid (Aβ) peptide is the primary constituent of neuritic plaques deposited extracellularly, whereas intraneuronal neurofibrillary tangles are mainly composed of hyperphosphorylated tau (P-tau) (Ross and Poirier, 2004). In AD-biomarker research, there is an almost complete consensus

Extracellular vesicles

EV research is an emerging field with increasing production of published data. The term EVs includes exosomes (EXs), microvesicles (MVs), and ectosomes released from different cell types and found in several body fluids (Carreras-Planella et al., 2017, Gámez-Valero et al., 2015, Raposo and Stoorvogel, 2013). Although EVs and specifically EXs were initially considered a cellular garbage disposal mechanism, EVs are nowadays widely accepted as principal players in intercellular communication and

Conclusions

In recent years, we have seen a considerable increase in research into EVs and a corresponding deepening of our understanding. As well as their fundamental aspects, their suitability as sources of biomarkers or therapeutic tools is also being explored. It has been proven that neurons and other cells of the CNS are able to produce EVs. Currently, there is a significant interest in the study of the vesicular content from different tissues and fluids for dementia-related NDDs to identify

Disclosure statement

The authors report no conflicts of interest.

Acknowledgements

The authors especially express gratitude to Laura Carreras-Planella for her graphic art contribution. This work was supported by Spain's Ministry of Health FIS grant PI15/216 and the MaratóTV3 grant 1405/10. AG-V is sponsored by a grant (482/U/2014) from Fundació La Marató TV3.

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