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Lipid Metabolic Alterations in the ALS–FTD Spectrum of Disorders
Open accessAbstract
There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in particular in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In ALS these alterations are well described and evident not only with the progression of the disease but also years before diagnosis. Still, there are some discrepancies in findings relating to the causal nature of lipid metabolic alterations, partly due to the great clinical heterogeneity in ALS. ALS presentation is within a disorder spectrum with Frontotemporal Dementia (FTD), and many patients present mixed forms of ALS and FTD, thus increasing the variability. Lipid metabolic and other systemic metabolic alterations have not been well studied in FTD, or in ALS–FTD mixed forms, as has been in pure ALS. With the recent development in lipidomics and the integration with other -omics platforms, there is now emerging data that not only facilitates the identification of biomarkers but also enables understanding of the underlying pathological mechanisms. Here, we reviewed the recent literature to compile lipid metabolic alterations in ALS, FTD, and intermediate mixed forms, with a view to appraising key commonalities or differences within the spectrum.
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CE(20:4) is one of the most abundant CE species in human plasma.
“Given that CE(20:4) is one of the most abundant CE species in human plasma34, we measured CE(20:4) levels in human CSF samples and detected elevated CE(20:4) in AD patients compared to age-matched control (Figure S5A).”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [34]
Cholesterol dysregulation and lipid dyshomeostasis have been identified in several neurodegenerative diseases.
“Importantly, cholesterol dysregulation6–9 and lipid dyshomeostasis8,10–15 have been identified in several neurodegenerative diseases.”
From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [15]
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Lipidomics Analysis of Behavioral Variant Frontotemporal Dementia: A Scope for Biomarker Development
Kim, W. S., Jary, E., Pickford, R., He, Y., Ahmed, R. M., Piguet, O., Hodges, J. R., & Halliday, G. M. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00104 · Cited by 50
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Dysregulated Brain Cholesterol Metabolism Is Linked to Neuroinflammation in Huntington's Disease
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Cholesterol dyshomeostasis in amyotrophic lateral sclerosis: cause, consequence, or epiphenomenon?
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Altered High Density Lipoprotein Composition in Behavioral Variant Frontotemporal Dementia
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Disruption of orbitofrontal-hypothalamic projections in a murine ALS model and in human patients
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Increased VLCFA-lipids and ELOVL4 underlie neurodegeneration in frontotemporal dementia
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Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis
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Anthropometric measures are not accurate predictors of fat mass in ALS
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Dyslipidemia in patients with amyotrophic lateral sclerosis – a case control retrospective study
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Neural networks associated with body composition in frontotemporal dementia
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Body Complexion and Circulating Lipids in the Risk of TDP-43 Related Disorders
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Self-citationLipid metabolism in adipose tissue
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Whole-Exome Sequencing and C9orf72 Analysis in Primary Progressive Aphasia
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Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91
“10 Given that CE(20:4) is one of the most abundant CE species in human plasma, 34 we measured CE(20:4) levels in human cerebrospinal fluid (CSF) samples and detected elevated CE(20:4) in AD patients compared with age-matched control (Figure S5A).”
Evidence of Metabolic Dysfunction in Amyotrophic Lateral Sclerosis (ALS) Patients and Animal Models
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Neural Metabolic Networks: Key Elements of Healthy Brain Function
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In vivo diagnosis of TDP-43 proteinopathies: in search of biomarkers of clinical use
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Lipid mediated brain disorders: A perspective
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Genetic evidence for the liver-brain axis: lipid metabolism and neurodegenerative disease risk
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Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs
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GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau
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Evidence of mitochondrial dysfunction in ALS and methods for measuring in model systems
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CETP inhibitor evacetrapib enters mouse brain tissue
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Free fatty acids support oligodendrocyte survival in a mouse model of amyotrophic lateral sclerosis
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Network spreading and local biological vulnerability in amyotrophic lateral sclerosis
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Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like CellsPreprint
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TDP-43 and ALS - what's wrong with my membranes?
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Metadata
- Authors
- Godoy-Corchuelo, J. M., Fernández-Beltrán, L. C., Ali, Z., Gil-Moreno, M. J., López-Carbonero, J. I., Guerrero-Sola, A., Larrad-Sainz, A., Matias-Guiu, J., Matias-Guiu, J. A., Cunningham, T. J., & Corrochano, S.
- Affiliations
- Hospital Clínico San Carlos (ES)
- Mary Lyon Centre at MRC Harwell (GB)
- Neurological Disorders Group, Hospital Clínico San Carlos, IdISSC, 28040 Madrid, Spain
- Nutrition and Endocrinology Group, Hospital Clínico San Carlos, IdISSC, 28040 Madrid, Spain
- Corresponding author
- Corrochano, Silvia
- ORCID
- Venue
- Biomedicines
- Publisher
- MDPI AG
- Published
- 2022-05-10
- Volume
- 10
- Issue
- 5
- Pages
- 1105
- ISSN
- 2227-9059 (ISSN-L)
- PMC
- PMC9138405
- OpenAlex
- W4280562517
- Cited by
- 35
- References
- 125
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 1
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Docta Complutense (Universidad Complutense de Madrid) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Consejería de Educación de la Comunidad de Madrid (2018-T1/BMD-10731, PDI2020-1153-70RB-100)
- Spanish Minister of Science (2018-T1/BMD-10731, PDI2020-1153-70RB-100)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- amyotrophic lateral sclerosis, frontotemporal dementia, lipid metabolism, lipidomics, neurodegeneration, biomarkers
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