ArticleProceedings of the National Academy of Sciences of the United States of America2004
Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 542 papers, 2 of them syntheses that pooled it.
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Who cites it
542 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,140 citations in OpenAlex.
- Sphingolipids associated research in Alzheimer's disease: an explored trends analysis.Frontiers in aging neuroscience · 2026Pooled it
- GPBP or CERT: The Roles in Autoimmunity, Cancer or Neurodegenerative Disease-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Improvements in high-yield detection and localisation of cholesterol in murine brains using water cluster beam secondary ion mass spectrometry.Analytical and bioanalytical chemistry · 2026Article
- The Interplay of Metabolic Dysfunction, Neuroinflammation, and Mitochondrial Dysfunction in Balance Impairment: Insights from Type 2 Diabetes Mellitus and Alzheimer's Disease.Molecular neurobiology · 2026Review
- Circulating Metabolite Signatures Associated With Amyloid Positivity, Cognitive Performance and Plasma P-tau181 Levels in Cognitively Unimpaired Older Adults.Molecular neurobiology · 2026Article
- Trained immunity links hematopoietic stem cell aging to aging-associated inflammation.Nature aging · 2026Article
- Development of a FRET-Based Assay for Human Neutral Sphingomyelinase 2.Biochemistry · 2026Article
- Lipid Oxidation Effect on Membrane Properties in Phosphatidylinositol- and Phosphatidylserine-Enriched Neuronal Biomimetic Models.The journal of physical chemistry. B · 2026Article
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- The protective effects of dexmedetomidine via AMPK/SIRT1 pathway activation in a rat model of alzheimer's disease: evidence from preliminary findings.Molecular biology reports · 2026Article
- Lipidomic and sterolomic profiles of different brain regions in the mouse model of Alzheimer's disease.Neural regeneration research · 2026Article
- Application of Plasma Metabolomic Biomarker Panels in Early Diagnosis and Disease Staging of Alzheimer's Disease.Metabolites · 2026Article
- The role of lipid metabolism in neuronal senescence.FEBS open bio · 2026Review
- Plasma ceramide mediates the association of peripheral T cells with Alzheimer's disease.Journal of advanced research · 2026Article
- Circulating Sphingomyelins Correlate With Plasma T-Tau in Cognitively Unimpaired Older Adults at Risk of Developing Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Spatial-temporal lipidomics reveals dysregulated lipid metabolism in mouse brain during Alzheimer's disease progression.Journal of advanced research · 2026Article
- Dietary silver nanoparticle supplementation induces Alzheimer-like lesions through Bifidobacterium deficiency-dominated gut microbiota dysbiosis and neuroinflammation.NPJ science of food · 2026Article
- Peripheral Insulin Resistance and Alzheimer's Disease: Possible Mediators Including Extracellular Vesicles.Geriatrics & gerontology international · 2026Review
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- Fingolimod normalizes metabolic signatures associated with synaptic plasticity and memory in APP/PS1 model: Sphingosine-1-phosphate receptor a therapeutic target for Alzheimer's.Scientific reports · 2026Article
482 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid beta-peptide (Abeta) and degeneration of neurons in brain regions such as the hippocampus, resulting in progressive cognitive dysfunction. The pathogenesis of AD is tightly linked to Abeta deposition and oxidative stress, but it remains unclear as to how these factors result in neuronal dysfunction and death. We report alterations in sphingolipid and cholesterol metabolism during normal brain aging and in the brains of AD patients that result in accumulation of long-chain ceramides and cholesterol. Membrane-associated oxidative stress occurs in association with the lipid alterations, and exposure of hippocampal neurons to Abeta induces membrane oxidative stress and the accumulation of ceramide species and cholesterol. Treatment of neurons with alpha-tocopherol or an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and cholesterol and protects them against death induced by Abeta. Our findings suggest a sequence of events in the pathogenesis of AD in which Abeta induces membrane-associated oxidative stress, resulting in perturbed ceramide and cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that leads to clinical disease.
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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.