Extracellular Vesicles in Alzheimer’s and Parkinson’s Disease: Small Entities with Large Consequences

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are incurable, devastating neurodegenerative disorders characterized by the formation and spreading of protein aggregates throughout the brain. Although the exact spreading mechanism is not completely understood, extracellular vesicles (EVs) have been proposed as potential contributors. Indeed, EVs have emerged as potential carriers of disease-associated proteins and are therefore thought to play an important role in disease progression, although some beneficial functions have also been attributed to them. EVs can be isolated from a variety of sources, including biofluids, and the analysis of their content can provide a snapshot of ongoing pathological changes in the brain. This underlines their potential as biomarker candidates which is of specific relevance in AD and PD where symptoms only arise after considerable and irreversible neuronal damage has already occurred. In this review, we discuss the known beneficial and detrimental functions of EVs in AD and PD and we highlight their promising potential to be used as biomarkers in both diseases.

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

“…α-Synuclein in oligomerized or aggregated form is known to be released outside from the neurons packed in extracellular vesicles (EVs), and such EVs may be responsible for the neuron-to-neuron transfer of α-synuclein and the spread of PD pathogenesis in the brain ( Lööv et al, 2016 ; Yu et al, 2020 ). The EVs from the brain likewise may carry toxic oligomeric α-synuclein to the peripheral circulation, and some studies examined the biomarker potential of EV-α-synuclein in blood ( Vandendriessche et al, 2020 ; Yu et al, 2020 ). For the latter purpose, α-synuclein present in neuron-derived EVs, positive for neuronal cell adhesion molecule LCAM1, were analyzed ( Lööv et al, 2016 ; Vandendriessche et al, 2020 ).…”

“…The EVs from the brain likewise may carry toxic oligomeric α-synuclein to the peripheral circulation, and some studies examined the biomarker potential of EV-α-synuclein in blood ( Vandendriessche et al, 2020 ; Yu et al, 2020 ). For the latter purpose, α-synuclein present in neuron-derived EVs, positive for neuronal cell adhesion molecule LCAM1, were analyzed ( Lööv et al, 2016 ; Vandendriessche et al, 2020 ). Thus, a large study measured α-synuclein content in plasma as well as in LCAM1 positive EVs isolated from the blood of 267 PD and 215 controls; the plasma levels of α-synuclein did not differ in the groups, but LCAM1 positive EV-α-synuclein was significantly higher in the PD cases compared to that in the controls ( Shi et al, 2014 ).…”

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

“…During the following years, the number of EV publications grew progressively [14][15][16]. Recent knowledge about the role of EVs in Alzheimer's [96,97] has been chosen as a main focus of the present review. The data presented concern primarily the relevant EV details identified recently.…”

Brain-Derived Extracellular Vesicles in Health and Disease: A Methodological Perspective

“…However, it is still not clear if, in humans (where neurodegenerative diseases last for years), EVs are relevant disease propagators or rather represent a failed mechanism of clearing misfolded proteins, such as Aβ [55], or whether both aspects hold true to some degree [35]. Of note, EVs in the context of neurodegenerative diseases have also been extensively studied and discussed as potential biomarkers [36,56,57].…”