ArticleJournal of Alzheimer's disease : JAD2022
Oxysterols and Oxysterol Sulfates in Alzheimer's Disease Brain and Cerebrospinal Fluid.
Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- A Validated Mass Spectrometry Platform for Oxysterol Analysis of Single Human Gastruloids and Liver Organoids.Analytical chemistry · 2026Article
- Dietary mixed-oxysterols and 27-Hydroxycholesterol induce cognitive impairment by regulating gut microbiota and miR-144-3p in vivo.GeroScience · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- 27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine.npj aging · 2025Article
- Oxysterol-Induced Inflammation in Human Diseases: Strategies for Treatment with Natural Compounds and Synthetic Molecules.Molecules (Basel, Switzerland) · 2025Review
- The Link Between Oxysterols and Gut Microbiota in the Co-Dysfunction of Cognition and Muscle.Nutrients · 2025Article
- The pathophysiology of mixed Alzheimer's disease and vascular dementia.Theranostics · 2025Review
- Quantitative Determination of a Series of Oxysterols by an Optimized LC-MS/MS Analysis in Different Tissue Types.International journal of molecular sciences · 2024Article
- Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications?Essays in biochemistry · 2024Review
- Sulfation pathways in times of change.Essays in biochemistry · 2024Article
- Cholesterol profiling reveals 7β-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.Psychiatry and clinical neurosciences · 2024Article
- Oxysterols in Cell Viability, Phospholipidosis and Extracellular Vesicles Production in a Lung Cancer Model.Cell biochemistry and biophysics · 2024Article
- Accumulation of neutral lipids in dystrophic neurites surrounding amyloid plaques in Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- LC-MS Approaches for Oxysterols in Various Biosamples.Advances in experimental medicine and biology · 2024Article
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- 25-Hydroxycholesterol in health and diseases.Journal of lipid research · 2024Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBrain cholesterol levels are tightly regulated but increasing evidence indicates that cholesterol metabolism may drive Alzheimer's disease (AD)-associated pathological changes. Recent advances in understanding of mitochondrial dysfunction in AD brain have presented a vital role played by mitochondria in oxysterol biosynthesis and their involvement in pathophysiology. Oxysterol accumulation in brain is controlled by various enzymatic pathways including sulfation. While research into oxysterol is under the areas of active investigation, there is less evidence for oxysterol sulfate levels in human brain.
objectiveThis study investigates the hypothesis that AD brain oxysterol detoxification via sulfation is impaired in later stages of disease resulting in oxysterol accumulation.
methodsLipids were extracted from postmortem frozen brain tissue and cerebrospinal (CSF) from late- (Braak stage III-IV) and early- (Braak stage I-II) stage AD patients. Samples were spiked with internal standards prior to lipid extraction. Oxysterols were enriched with a two-step solid phase extraction using a polymeric SPE column and further separation was achieved by LC-MS/MS.
resultsOxysterols, 26-hydroxycholesterol (26-OHC), 25-hydroxycholesterol (25-OHC), and 7-oxycholesterol levels were higher in brain tissue and mitochondria extracted from late-stage AD brain tissue except for 24S-hydroxycholesterol, which was decreased in late AD. However, oxysterol sulfates are significantly lower in the AD frontal cortex. Oxysterols, 25-OHC, and 7-oxocholesterol was higher is CSF but 26-OHC and oxysterol sulfate levels were not changed.
conclusionOur results show oxysterol metabolism is altered in AD brain mitochondria, favoring synthesis of 26-OHC, 25-OHC, and 7-oxocholesterol, and this may influence brain mitochondrial function and acceleration of the disease.
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