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Characterization of brain-derived extracellular vesicle lipids in Alzheimer's disease.
J Extracell Vesicles. 2021 05; 10(7):e12089.JE

Abstract

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.

Authors+Show Affiliations

The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia. Department of Biochemistry and Pharmacology The University of Melbourne Parkville Victoria Australia.Department of Biochemistry and Pharmacology The University of Melbourne Parkville Victoria Australia.The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne Parkville Victoria Australia.The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia.Department of Biochemistry and Genetics La Trobe Institute for Molecular Science, La Trobe University Bundoora Victoria Australia.The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia.Department of Biochemistry and Pharmacology The University of Melbourne Parkville Victoria Australia. School of Chemistry, Bio21 Molecular Science and Biotechnology Institute The University of Melbourne Parkville Victoria Australia.The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia. Department of Surgery, The Royal Melbourne Hospital The University of Melbourne Parkville Victoria Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34012516

Citation

Su, Huaqi, et al. "Characterization of Brain-derived Extracellular Vesicle Lipids in Alzheimer's Disease." Journal of Extracellular Vesicles, vol. 10, no. 7, 2021, pp. e12089.
Su H, Rustam YH, Masters CL, et al. Characterization of brain-derived extracellular vesicle lipids in Alzheimer's disease. J Extracell Vesicles. 2021;10(7):e12089.
Su, H., Rustam, Y. H., Masters, C. L., Makalic, E., McLean, C. A., Hill, A. F., Barnham, K. J., Reid, G. E., & Vella, L. J. (2021). Characterization of brain-derived extracellular vesicle lipids in Alzheimer's disease. Journal of Extracellular Vesicles, 10(7), e12089. https://doi.org/10.1002/jev2.12089
Su H, et al. Characterization of Brain-derived Extracellular Vesicle Lipids in Alzheimer's Disease. J Extracell Vesicles. 2021;10(7):e12089. PubMed PMID: 34012516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of brain-derived extracellular vesicle lipids in Alzheimer's disease. AU - Su,Huaqi, AU - Rustam,Yepy H, AU - Masters,Colin L, AU - Makalic,Enes, AU - McLean,Catriona A, AU - Hill,Andrew F, AU - Barnham,Kevin J, AU - Reid,Gavin E, AU - Vella,Laura J, Y1 - 2021/05/11/ PY - 2020/08/04/received PY - 2021/03/29/revised PY - 2021/04/13/accepted PY - 2021/5/20/entrez PY - 2021/5/21/pubmed PY - 2021/5/21/medline KW - Alzheimer's disease KW - brain KW - exosomes KW - extracellular vesicles KW - frontal cortex KW - glycerophospholipids KW - lipid biomarkers KW - lipidome KW - polyunsaturated fatty acids KW - sphingolipids KW - tissue SP - e12089 EP - e12089 JF - Journal of extracellular vesicles JO - J Extracell Vesicles VL - 10 IS - 7 N2 - 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. SN - 2001-3078 UR - https://www.unboundmedicine.com/medline/citation/34012516/Characterization_of_brain_derived_extracellular_vesicle_lipids_in_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -