ReviewExtracellular vesicles, new actors in the search for biomarkers of dementias
Graphical abstract
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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