ArticleScientific reports2021
Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Astrocytic lipid dysregulation as an early driver of neurodegeneration.Nature reviews. Neurology · 2026Review
- Ultra-rare variants in LAMA2 are risk factors for frontotemporal dementia and motor neuron disease.Human molecular genetics · 2026Article
- Elovanoid neuroprotection targets cell transcriptomics and proteomics to sustain synaptic integrity after brain injury.Communications biology · 2026Article
- Plasma complex lipids in relation to cortical thickness and brain volumes: results from the population-based Rhineland study.Lipids in health and disease · 2026Article
- Unveiling ribosomal dysfunction and impaired signaling pathways in the cortical region of 5xFAD mice.Acta neuropathologica communications · 2026Article
- From lipid function to dysfunction: Very long-chain fatty acids as emerging regulators of neuroinflammatory pathways.iScience · 2026Review
- Regulation of pexophagy by a novel TBK1-MARCHF7-PXMP4-NBR1 axis in PEX1-depleted HeLa cells.Autophagy · 2026Article
- Sex- and Regio-Specific Lipid Profiling of Shishamo and Capelin Fish by Nontargeted Liquid Chromatography/Mass Spectrometry.Foods (Basel, Switzerland) · 2026Article
- Glycosphingolipids in Dementia: Insights from Mass Spectrometry and Systems Biology Approaches.Biomedicines · 2025Review
- Implications of Fatty Acids for Age-Related Macular Degeneration: Evidence and Recommendations.Cells · 2025Review
- Differential effect of an evolving amyloid and tau pathology on brain phospholipids and bioactive lipid mediators in rat models of Alzheimer-like pathology.Journal of neuroinflammation · 2024Article
- Neuroinflammation is dependent on sex and ovarian hormone presence following acute woodsmoke exposure.Scientific reports · 2024Article
- A gram-scale synthesis of very-long chain polyunsaturated fatty acids (VLC-PUFAs).Organic & biomolecular chemistry · 2024Article
- ABCD1 Transporter Deficiency Results in Altered Cholesterol Homeostasis.Biomolecules · 2023Article
- Understanding the Roles of Very-Long-Chain Polyunsaturated Fatty Acids (VLC-PUFAs) in Eye Health.Nutrients · 2023Review
- Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.Brain communications · 2023Article
- Lipid Metabolic Alterations in the ALS-FTD Spectrum of Disorders.Biomedicines · 2022Review
- Sex-specific lipid dysregulation in theBrain communications · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Rare, yet biologically critical, lipids that contain very long chain fatty acids (VLCFA-lipids) are synthesized in the brain by the enzyme ELOVL4. High levels of VLCFA-lipids are toxic to cells and excess VLCFA-lipids are actively removed by ABCD1 in an ATP-dependent manner. Virtually nothing is known about the impact of VLCFA-lipids in neurodegenerative diseases. Here, we investigated the possible role of VLCFA-lipids in frontotemporal dementia (FTD), which is a leading cause of younger-onset dementia. Using quantitative discovery lipidomics, we identified three VLCFA-lipid species that were significantly increased in FTD brain compared to controls, with strong correlations with ELOVL4. Increases in ELOVL4 expression correlated with significant decreases in the membrane-bound synaptophysin in FTD brain. Furthermore, increases in ABCD1 expression correlated with increases in VLCFA-lipids. We uncovered a new pathomechanism that is pertinent to understanding the pathogenesis of FTD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.