Finding a novel method to understand the role of salivary exosome in progression of cognitive impairment to Alzheimer's disease: Biomarkers (non‐neuroimaging) / method development and/or quality control. (7th December 2020)

• Record Type: Journal Article
• Authors: Rastogi, Simran; Rani, Komal; Nikolajeff, Fredrik; Kumar, Saroj
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.041920
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: 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.