Oral Presentation Australasian Extracellular Vesicles Conference 2020

Uncovering the role of brain derived exosomal lipids in Alzheimer’s disease (#3)

Huaqi Su 1 , Adityas Purnianto 1 , Kevin Barnham 1 2 , Gavin Reid 2 , Laura Vella 1 2
  1. The Florey Institute of Neuroscience and Mental Health, Melbourne , VIC, Australia
  2. The University of Melbourne, Parkville, VIC, Australia

Lipid dysregulation is associated with Alzheimer’s disease (AD) pathogenesis, however the application of lipids as blood-based biomarkers of AD, has proven difficult. Most biomarker studies have focused on examining the entire lipidome, without focusing on brain-specific lipids. Exosomes are small vesicles released from cells and tissues (including the brain) into the periphery, carrying a subset of lipids which make them uniquely suited for biomarker exploration.

To determine the potential of exosomal lipids as biomarkers, here, using the protocol developed for brain-derived exosome isolation and characterization (Vella, et al. JEV. 2017) and quantitative mass spectrometry based lipidome analysis (Rustam and Reid. Anal. Chem. 2018), we describe the lipidomic characterization of post-mortem frontal cortex derived exosomes from AD subjects versus neurological controls, and their parental tissues.

Western blot result showed enrichment of syntenin and TSG101 in isolated exosomes fractions, and little calnexin was detected, indicating minimum cell lysis. TEM revealed the typical round and cup-shaped exosome morphology and vesicle size being 50-150nm. Lipidome analysis identified and quantified approximately 500 lipids. Enrichment and remodeling of multiple lipid classes and subclasses were observed in the exosomes, including glycerophospholipids and sphingolipids. Meanwhile, remodeling in phosphatidylethanoamine (PE) lipid class was observed in AD exosomes in comparison to control exosomes.

Many of these changes in exosomes have previously been reported to play key roles in AD pathogenesis, suggesting brain-derived exosomes provide a readout of lipid dysregulation in AD and highlighting the potential use of these lipids as disease biomarkers.