Summary of project PR002351

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002351. The data can be accessed directly via it's Project DOI: 10.21228/M8R53K This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR002351
Project DOI:doi: 10.21228/M8R53K
Project Title:Characterization of brain‐derived extracellular vesicle lipids in Alzheimer's disease
Project Type:MS lipidomic quantitative analysis
Project Summary:Lipid dyshomeostasis is associated with the most common form of dementia, Alzheimer's disease (AD). Substantial progress has been made in identifying positron emission tomography and cerebrospinal fluid biomarkers for AD, but they have limited use as front‐line diagnostic tools. Extracellular vesicles (EVs) are released by all cells and contain a subset of their parental cell composition, including lipids. EVs are released from the brain into the periphery, providing a potential source of tissue and disease specific lipid biomarkers. However, the EV lipidome of the central nervous system is currently unknown and the potential of brain‐derived EVs (BDEVs) to inform on lipid dyshomeostasis in AD remains unclear. The aim of this study was to reveal the lipid composition of BDEVs in human frontal cortex, and to determine whether BDEVs have an altered lipid profile in AD. Using semi‐quantitative mass spectrometry, we describe the BDEV lipidome, covering four lipid categories, 17 lipid classes and 692 lipid molecules. BDEVs were enriched in glycerophosphoserine (PS) lipids, a characteristic of small EVs. Here we further report that BDEVs are enriched in ether‐containing PS lipids, a finding that further establishes ether lipids as a feature of EVs. BDEVs in the AD frontal cortex offered improved detection of dysregulated lipids in AD over global lipid profiling of this brain region. AD BDEVs had significantly altered glycerophospholipid and sphingolipid levels, specifically increased plasmalogen glycerophosphoethanolamine and decreased polyunsaturated fatty acyl containing lipids, and altered amide‐linked acyl chain content in sphingomyelin and ceramide lipids relative to CTL. The most prominent alteration was a two‐fold decrease in lipid species containing anti‐inflammatory/pro‐resolving docosahexaenoic acid. The in‐depth lipidome analysis provided in this study highlights the advantage of EVs over more complex tissues for improved detection of dysregulated lipids that may serve as potential biomarkers in the periphery.
Institute:The University of Melbourne
Department:The Florey Institute of Neuroscience and Mental Health
Last Name:Su
First Name:Huaqi
Address:30 Royal Parade, Melbourne, VIC, 3150, Australia
Email:huaqi.su@unimelb.edu.au
Phone:+61416373787

Summary of all studies in project PR002351

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
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(* : Contains raw data)
ST003769 Characterization of brain‐derived extracellular vesicle lipids in Alzheimer's disease Homo sapiens University of Melbourne MS 2025-03-25 1 32 Uploaded data (3.5G)*
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