Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

A 'Systems-omics' Strategy to Uncover the Role of Brain Tissue Derived Exosomal Lipids in Alzheimer’s Disease (#209)

Huaqi (Kate) Su 1 2 , Kevin J Barnham 1 2 , Laura J Vella 2 , Gavin E Reid 1
  1. The University of Melbourne, Parkville, VIC, Australia
  2. Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia

Lipid dysregulation is known to be associated with Alzheimer’s disease (AD) pathogenesis. Exosomes (40-100 nm vesicular bodies) play key roles in effecting phenotypic changes upon fusion or uptake by a recipient cell. However, while exosomal membrane lipids and bioactive lipid cargo are expected to play pivotal roles in exosome secretion, fusion and uptake, and in target cell functional response, detailed characterization of the lipidomes of exosomes secreted from brain tissue of AD patients, and exploration of their functional roles, has not yet been explored. Here, using workflows recently developed for extracellular vesicle secretion, isolation and characterization (Vella, et al. J. Extracell. Vesicles. 2017, 6, 1348885) and quantitative mass spectrometry based lipidome analysis (Rustam and Reid. Anal. Chem., 2018, 90, 374–397.), the lipidome compositions of exosomes released by post-mortem frontal cortex brain tissue from a series of AD patients versus healthy controls, and their parental tissues, were acquired. Proteomic analysis of these samples was also performed to enable a 'systems-omics' evaluation of the key lipid metabolism pathways associated with AD pathogenesis. From this study, approx. 400 lipids were identified and quantified in each sample. Enrichment and remodelling of multiple exosome lipid classes and subclasses were observed, including glycerophospholipids and sphingolipids . Many of these changes have previously been reported to play key roles in the regulation of physiological processes relevant to AD pathogenesis. These results establish a foundation for future investigations of brain-derived exosome lipids as potential biomarkers for AD diagnosis and for the development of novel therapeutic agents acting through relevant lipid pathways for the treatment of this disorder.