Uncovering pathophysiological changes in frontotemporal dementia using serum lipids.

Katherine Phan, Ying He, Russell Pickford, Surabhi Bhatia, Jared S Katzeff, John R Hodges, Olivier Piguet, Glenda M Halliday, Woojin Scott Kim

Journal: Scientific reports 2020;10(1):3640

PMID: 32107421

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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.

Address: The University of Sydney, Brain and Mind Centre & Central Clinical School, Sydney, NSW, Australia.; Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia.; ARC Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia.; The University of Sydney, Brain and Mind Centre & School of Psychology, Sydney, NSW, Australia.; Neuroscience Research Australia, Sydney, NSW, Australia.; The University of Sydney, Brain and Mind Centre & Central Clinical School, Sydney, NSW, Australia. [email protected].; ARC Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia. [email protected].; The University of Sydney, Brain and Mind Centre & School of Psychology, Sydney, NSW, Australia. [email protected].; Neuroscience Research Australia, Sydney, NSW, Australia. [email protected].; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. [email protected].; The University of Sydney, Brain and Mind Centre & Central Clinical School, Sydney, NSW, Australia. [email protected].; Neuroscience Research Australia, Sydney, NSW, Australia. [email protected].; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. [email protected].

DOI: 10.1038/s41598-020-60457-w

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MeSH Terms: Aged, Biomarkers, Female, Frontotemporal Dementia, Humans, Lipids, Male, Middle Aged