Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia

• DOI: 10.1038/s41598-021-00870-x
• Publication Date: 2021-11-01T11:04:13Z
• Authors: Ying He; Katherine Phan; Surabhi Bhatia; Russell Pickford; YuHong Fu; Yue Yang; John R. Hodges; Olivier Piguet; Glenda M. Halliday; Woojin Scott Kim
• Keywords: Pathogenesis

Abstract Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by enzyme ELOVL4. High levels of VLCFA-lipids toxic to cells and excess actively removed ABCD1 an ATP-dependent manner. Virtually nothing is known about impact neurodegenerative diseases. Here, we investigated possible role frontotemporal dementia (FTD), which a leading cause younger-onset dementia. Using quantitative discovery lipidomics, identified three VLCFA-lipid species were significantly increased FTD compared controls, with strong correlations Increases ELOVL4 expression correlated significant decreases membrane-bound synaptophysin brain. Furthermore, increases VLCFA-lipids. We uncovered new pathomechanism pertinent understanding pathogenesis FTD.