Using spatial transcriptomics to investigate region‐specific gene expression in J20 mice

Abstract

AbstractBackgroundAlzheimer’s disease (AD) and dementia with Lewy bodies (DLB) share various pathological and symptomatic traits. As such, providing an accurate diagnosis of DLB can be difficult, ultimately impacting patient support and care. It is therefore imperative to establish biomarkers which reliably differentiate between disease states. Plasma‐derived exosomes appear to be promising in this regard. Exosomes are extracellular vesicles, containing cargos from the cell from which they originate. Increased concentrations of exosomal disease‐associated proteins, such as p‐T181‐tau and Aβ‐42, have previously been associated with cognitive decline and disease progression among AD patients (Winston et al., 2016; Kapogiannis et al., 2019).MethodWe aim to quantify exosome‐associated proteins from AD patients, DLB patients and healthy controls in order to establish exosomal signatures to differentiate between disease states. Exosomes are being isolated using differential ultracentrifugation. Nanoparticle track analysis (NTA) and western blots are being used to verify isolation, and ELISA assays against p‐T181‐tau, Aβ‐42 and α‐synuclein will be used to quantify proteins of interest. Plasma samples are being collected at baseline and after a 6 month follow‐up period in order to monitor the stability of these potential biomarkers.ResultTo date, full ethics approval has been granted for this study, and the differential ultracentrifugation protocol has been established. Successful isolation of particles in the size range of exosomes (30 – 100nm) has been confirmed using NTA. ELISA assays will be undertaken in the up‐coming months, with the aim of collecting and analysing baseline results by May 2023.ConclusionExosomes already appear to be a reliable, and relatively non‐invasive biomarker for assessing disease state and progression among dementia patients. Our preliminary findings have shown successful isolation, and we believe the findings could be invaluable with regards to improved diagnosis options for DLB.