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Front. Neurol. | doi: 10.3389/fneur.2018.00104

Lipidomics analysis of behavioral variant frontotemporal dementia: a scope for biomarker development

 Woojin Kim1*, Eve Jary1,  Russell Pickford2, Ying He1, Rebekah Ahmed1,  Olivier Piguet1, John Hodges1 and Glenda Halliday1
  • 1University of Sydney, Australia
  • 2University of New South Wales, Australia

Behavioral variant frontotemporal dementia (bvFTD) is the most prevalent form of FTD syndromes. bvFTD is characterized clinically by changes in behavior and cognition, and pathologically by focal brain atrophy and concomitant loss of lipids. bvFTD is further characterized by eating abnormalities that result in dyslipidemia. Although dyslipidemia is apparent in bvFTD, very little is known about global lipid changes in bvFTD and lipid dysregulation underlying bvFTD. Here, we undertook a comprehensive lipidomics analysis of blood plasma from patients with bvFTD, patients with Alzheimer’s disease and controls, using liquid chromatography-tandem mass spectrometry, with the aim of understanding lipid dysregulation in bvFTD. In our analysis, we detected all four major classes of lipids (glycerolipids, phospholipids, sphingolipids, sterols), 17 subclasses of lipids and 3,225 putative individual lipid species in total, as well as a group of dietary lipids. We found that the levels of numerous lipid species were significantly altered in bvFTD compared to AD and control. We found that the total abundance of triglyceride increased significantly in bvFTD, whereas phosphatidylserine and phosphatidylglycerol decreased significantly in bvFTD. These results suggest manifestation of hypertriglyceridemia and hypoalphalipoproteinemia in bvFTD. We also identified five lipid molecules – triglyceride (16:0/16:0/16:0), diglyceride (18:1/22:0), phosphatidylcholine (32:0), phosphatidylserine (41:5) and sphingomyelin (36:4) – that could potentially be used for developing biomarkers for bvFTD. Furthermore, an analysis of plant lipids revealed significant decreases in monogalactosyldiacylglycerol and sitosteryl ester in bvFTD, indicating altered eating behavior in bvFTD. This study represents the first lipidomics analysis of bvFTD and has provided new insights into an unrecognized perturbed pathology in bvFTD, providing evidence in support of considerable lipid dysregulation in bvFTD.

Keywords: Frontotemporal Dementia, Lipids, Dyslipidemia, lipidomics, Alzheimer’s disease, biomarker, Hypertriglyceridemia

Received: 30 Nov 2017; Accepted: 13 Feb 2018.

Edited by:

Tibor Hortobágyi, University of Debrecen, Hungary

Reviewed by:

Claus J. Scholz, University of Bonn, Germany
Tamas Fulop, Université de Sherbrooke, Canada
Anna M. Giudetti, University of Salento, Italy  

Copyright: © 2018 Kim, Jary, Pickford, He, Ahmed, Piguet, Hodges and Halliday. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Woojin Kim, University of Sydney, Sydney, Australia, woojin.kim@sydney.edu.au