Blood-derived exosomes for biomarker discovery in Alzheimer’s disease

• Main Author: Martins, Tânia Cristina Soares
• Publication Date: 2024
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10773/42363
• topic: Alzheimer’s disease; Biomarker; Blood; Diagnosis; Exosomes abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide, accounting for 60-70% of all dementia cases. It is estimated that the dementia cases will triplicate by 2050, alongside with increased life expectancy and aging population. AD differential diagnosis is difficult, particularly in early stages. The current available and widely accepted molecular tool for AD diagnosis is based on the monitoring of the gold-standard biomarker triplet, Aβ, Total-tau and P-tau 181 levels in cerebrospinal fluid, which is collected through an invasive procedure run at hospital settings, not being available at primary care centres. Therefore, the identification of biomarkers that could assist AD diagnosis in peripheral biofluids would represent an ideal tool, allowing the accessibility of AD diagnosis. Extracellular vesicles, namely exosomes, meet the criteria of useful sources of biomarkers since their cargo can reflect physiological and pathological stages, they can cross the blood-brain barrier and protect their content from degradation in bloodstream. Hence, in this PhD project distinct strategies were followed for the identification of putative biomarker candidates in blood-derived exosomes: i) bioinformatic analysis of exosomal proteomes retrieved from databases; ii) characterization of exosome proteome and/or phosphoproteome in AD and iii) definition of exosomal metabolic profile in AD. The work presented allowed the identification of novel biomarker candidates and disease-related metabolic profiles that hold value in AD diagnosis. Further, this study also supports that exosome cargo can be involved in AD pathophysiological mechanisms. Taken together, data support the potential of exosomes as novel tools to assist in AD diagnosis.