The Evolving Landscape of Exosomes in Neurodegenerative Diseases: Exosomes Characteristics and a Promising Role in Early Diagnosis

Abstract

Neurodegenerative diseases (ND) remains to be one of the biggest burdens on healthcare systems and serves as a leading cause of disability and death. Alzheimer's disease (AD) is among the most common of such disorders, followed by Parkinson's disease (PD). The basic molecular details of disease initiation and pathology are still under research. Only recently, the role of exosomes has been linked to the initiation and progression of these neurodegenerative diseases. Exosomes are small bilipid layer enclosed extracellular vesicles, which were once considered as a cellular waste and functionless. These nano-vesicles of 30-150 nm in diameter carry specific proteins, lipids, functional mRNAs, and high amounts of non-coding RNAs (miRNAs, lncRNAs, and circRNAs). As the exosomes content is known to vary as per their originating and recipient cells, these vesicles can be utilized as a diagnostic biomarker for early disease detection. Here we review exosomes, their biogenesis, composition, and role in neurodegenerative diseases. We have also provided details for their characterization through an array of available techniques. Their updated role in neurodegenerative disease pathology is also discussed. Finally, we have shed light on a novel field of salivary exosomes as a potential candidate for early diagnosis in neurodegenerative diseases and compared the biomarkers of salivary exosomes with other blood/cerebrospinal fluid (CSF) based exosomes within these neurological ailments.

Keywords: Alzheimer’s disease; Parkinson’s disease; biomarkers; neurodegenerative diseases; salivary exosomes.

Figure 1

Schematic representation of key exosomal biomarkers in neurodegenerative diseases. Amyloid-beta (Aβ), amyloid precursor protein (APP), acetylcholinesterase (AChE), alpha-synuclein (α-syn), super-oxide dismutase 1 (SOD1), tar-DNA binding protein-43 (TDP-43), mutant huntingtin protein (mHtt), and micro RNAs (miRNAs).

Figure 2

Illustration showing key events in the process of exosome biogenesis including the compositional details of a mature exosome.

Figure 3

The neuropathological hallmarks of Alzheimer’s disease: (A) formation of amyloid-beta plaques (B) formation of neurofibrillary tangles.

Figure 4

Key differentiation in the normal physiological state and pathological state of dopamine metabolism and homeostasis of alpha-synuclein protein (α -syn) (A) the normal physiological state: Homeostasis of alpha-synuclein protein maintained (B) the perturbations in alpha-synuclein homeostasis as well interneuronal aggregation of α-syn oligomer and formation of lewy bodies.

Figure 5

Seeding of hallmark proteins in a prion-based manner by exosomes (A) the seeding of amyloid-beta and tau protein through exosomal cargo in Alzheimer’s disease (AD), dispersion of AD pathology. (B) the seeding of alpha-synuclein and tau protein in Parkinson’s disease (PD) through exosomal cargo, dispersion of PD pathology. The presence of all these prime proteins in the biofluid saliva after the exosomes cross the blood–brain barrier (BBB).