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.

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In recent years, studies on mineralized tissues are becoming increasingly popular not only due to the diverse mechanophysical properties of such materials but also because of the growing need to understand the intricate mechanism involved in their assembly and formation. The biochemical mechanism that results in the formation of such hierarchical structures through a well-coordinated accumulation of inorganic and organic components is termed biomineralization. Some prime examples of such tissues in the human body are teeth and bones. Our current study is an attempt to dissect the compositional details of the inorganic and organic components in four major types of human teeth using mass spectrometry-based approaches. We quantified inorganic materials using inductively coupled plasma resonance mass spectrometry (ICP-MS). Differential level of ten different elements, Iron (Fe), Cadmium (Cd), Potassium (K), Sulphur (S), Cobalt (Co), Magnesium (Mg), Manganese (Mn), Zinc (Zn), Aluminum (Al), and Copper (Cu) were quantified across different teeth types. The qualitative and quantitative details of their respective proteomic milieu revealed compositional differences. We found 152 proteins in total tooth protein extract. Differential abundance of proteins in different teeth types were also noted. Further, we were able to find out some significant protein-protein interaction (PPI) backbone through the STRING database. Since this is the first study analyzing the differential details of inorganic and organic counterparts within teeth, this report will pave new directions to the compositional understanding and development of novel in-vitro repair strategies for such biological materials.

Parkinson’s disease is generally asymptomatic at earlier stages. The pressing need is for the susceptibility risk biomarkers, that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of exosomes in progression of neurodegenerative diseases is already reported and its cargo could be potent in playing a revolutionary role in biomarker discovery. In our study, the salivary exosomes were efficiently isolated by chemical precipitation from subjects (PD = 70, healthy controls = 26 and probable PD = 08) followed by antibody-based validation through CD63, CD9, GAPDH, flotillin 1, L1CAM, and calnexin. Morphological characterization of the isolated exosomes through transmission elcetrom microscopy (TEM). The exosome quantification via fluorescence and antibody-based nanoparticle tracking analysis (NTA). The total alpha-synuclein (α-syntotal) in salivary exosomal cargo was quantified by ELISA. The disease severity staging confirmation was done by 99mTc-TRODAT-SPECT. We observed a significant increase in total exosome concentration in PD patients than the healthy control (HC) where fluorescence-tagged exosomes were observed to be higher in PD (p < 0.0001) than the HC using NTA with a sensitivity of 94.34%. This results was validated through exosomes tagged with antibody CD63 (p = 0.006) with a similar sensitivity of 94.12%. We further validated our findings with the ELISA-based α-syntotal concentration in exosomes where it was observed to be higher in PD with a sensitivity of 88.24%. The striatal binding ratios in 99mTc-TRODAT-SPECT shown positive correlation with fluorescent exosomes concentration r = 0.3000, α-syntotal concentration r = 0.8000. In this study for the first time we have found that the fluorescence tagged exosomes has potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.

Background Cognitive impairment is an prominent aspect of aging and a common accomplice of dementia. Majority of dementia cases are dictated by Alzheimer’s disease (AD) pathology. There are many neuroimaging and molecular biomarkers to differentiate between cognitive impairment and dementia however, these are either invasive or expensive; also, for a patient without any cognitive complain, it is impractical to use these as an early diagnostic tool. Currently, extra‐cellular vesicles like exosomes are widely researched as they carry signals of disease pathology in there protein cargos. Its release and uptake in case of Parkinson’s and AD is already explored. In this study, we have demonstrated a novel method: nanoparticle tracking analysis to investigate how salivary exosomes concentration can elucidate the correlation between CI and AD and that could open a new way for early and cost‐effective screening of this disease. Method The exosomes were isolated from saliva using chemical precipitation. Total salivary exosomes concentration was measured by nanoparticle tracking analysis followed by exosomal cargo protein validation through automated western blot system using amyloid‐beta (Aβ) oligomer, monomer, phospho‐tau antibody. Result The exosome were validated using electron microscopy and exosomal surface marker CD63 [Figure 1 A & B] and its neuronal origin through, CD171 antibody [Figure 1 C]. We observed a significant difference in salivary exosomal concentration in cognitively impaired and AD patients (p=0.0001) [Figure 1 D] compared to age matched healthy control using NTA. We further validated and correlated our NTA findings by observing the protein expression level of oligomer Aβ, p‐tau. The Aβ oligomer/fibril abundance (p=0.0291) [Figure 2 A, B, C], p‐tau (p=0.0325) [Figure 2 D, E] and Aβ protein abundance (p=0.0198) [Figure 2 F, G] was significantly high in AD and CI patients in comparison to healthy control. Conclusion We demonstrated for the first time that the salivary exosome concentration as well as the expression level of hallmark proteins is higher in cognitively impaired and AD patient than healthy control as well is in accordance with the disease severity staging. This study has a potential to be developed as an early, cost‐effective screening method for detection of disease severity stage.