PLATFORM DEVELOPMENT FOR THE BLOOD-BASED DETECTION OF ALZHEIMER’S DISEASE

Abstract

This thesis will explore development in the identification and measurement of brain-related biomarkers from blood, specifically biomarkers associated with extracellular vesicles. In addition, it will elaborate on recent developments in sensor technologies to address the inherent challenges in the detection and profile the diverse contents – different molecular types, quantities and organizational states – in extracellular vesicles. More importantly, it will introduce the amplified plasmonic exosome (APEX) platform, a newly developed dedicated detection platform that is size-matched for the detection of exosomes, designed to overcome numerous challenges of blood-based measurement of brain-related molecules. With the platform, we have demonstrated the association of Aβ proteins to EV surface membrane. Importantly, such extravesicular association of molecules with EVs could reveal additional biophysical properties of the bound molecules and/or the vesicles. Specifically, we found that the extravesicular association of Aβ proteins could reflect the aggregation states of the bound proteins, thereby enabling biophysical and biochemical subtyping of the associated biomarkers, to achieve more accurate blood-based characterization of neurodegenerative diseases.