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.
Highlights
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
We were interested in three key aspects of Frontotemporal dementia (FTD) pathophysiology that are relevant to neurodegeneration – mitochondrial dysfunction, inflammation, and oxidative stress
component 3 (C3) levels are associated with cognitive decline in FTD patients[39]. We found that both interleukin 6 (IL-6) and C3 levels were significantly increased in FTD compared to controls (Fig. 3H,I), supporting our lipid data
Summary
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. 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. Recent advances in lipidomics technology based on mass spectrometry have significantly improved the detection of a vast array of lipids present in blood serum It has allowed detection of small, yet significant, differences in lipid levels that are intrinsically linked to disease processes. Correlation studies have shown that TG levels are positively correlated with body mass index (BMI), whereas HDL cholesterol levels are negatively correlated with BMI11 Both TG and HDL cholesterol levels are correlated to eating behavior (fat intake) and measures of cognition and disease duration[13].
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