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Uncovering pathophysiological changes in frontotemporal dementia using serum lipids

Phan, Katherine, He, Ying, Pickford, Russell, Bhatia, Surabhi, Katzeff, Jared S., Hodges, John R., Piguet, Olivier, Halliday, Glenda M., Kim, Woojin Scott·2020·Scientific Reports
DOI 10.1038/s41598-020-60457-wPMC PMC7046653
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Abstract

Blood serum is enriched in lipids and has provided a platform to understand the pathogenesis of a number of human diseases with improved diagnosis and development of biomarkers. Understanding lipid changes in neurodegenerative diseases is particularly important because of the fact that lipids make up >50% of brain tissues. Frontotemporal dementia (FTD) is a common cause of early onset dementia, characterized by brain atrophy in the frontal and temporal regions, concomitant loss of lipids and dyslipidemia. However, little is known about the link between dyslipidemia and FTD pathophysiology. Here, we utilized an innovative approach – lipidomics based on mass spectrometry – to investigate three key aspects of FTD pathophysiology – mitochondrial dysfunction, inflammation, and oxidative stress. We analyzed the lipids that are intrinsically linked to neurodegeneration in serum collected from FTD patients and controls. We found that cardiolipin, acylcarnitine, lysophosphatidylcholine, platelet-activating factor, o-acyl-ω-hydroxy fatty acid and acrolein were specifically altered in FTD with strong correlation between the lipids, signifying pathophysiological changes in FTD. The lipid changes were verified by measurement of the common disease markers (e.g. ATP, cytokine, calcium) using conventional assays. When put together, these results support the use of lipidomics technology to detect pathophysiological changes in FTD.

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Metadata

Authors
Phan, K., He, Y., Pickford, R., Bhatia, S., Katzeff, J. S., Hodges, J. R., Piguet, O., Halliday, G. M., & Kim, W. S.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-02-27
Volume
10
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-020-60457-w
PMC
PMC7046653
Cited by
72
References
8
Language
en
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