Blog

The Fight Against Alzheimer’s Disease—Can Oxysterol Analysis Provide a New Avenue of Exploration for Alzheimer’s Disease Detection and Prevention?

oxysterols-impact-Alzheimers-disease

Alzheimer’s disease is a serious neurological disorder with no cure available. As the disease progresses, mental function deteriorates, and patients develop dementia and slowly lose access to memories.

The number of people globally diagnosed with dementia is expected to rise to 153 million by 2050, a 300% increase from 2019 rates.1 Aging populations and improved methods of detection contribute to that increase. Given the numbers, many stand to benefit from improved prevention and therapeutics.

Cholesterol in Alzheimer’s Disease Research

It is well documented that cholesterol levels impact the central nervous system and are related to acquired neurological conditions.2 Specifically, research has linked the etiopathogenesis of Alzheimer’s disease to abnormal sterol metabolism.2,3 Thus analysis of sterols and oxysterols can provide new insights into the origin and pathophysiology of Alzheimer’s disease, perhaps empowering therapies and diagnostics for the prediction and treatment of future cases.

Certain oxysterols are ligands to Liver X-activated receptors (LXR), and certain LXRs, when activated, reduce lipogenesis and cholesterol synthesis.2 Further, oxysterol metabolism impacts neuronal membrane plasticity, survival, and turnover, all of which can contribute to the progression of Alzheimer’s disease.2

Oxysterols’ Research Implications

More research is necessary to better leverage the measurement of oxysterols and their impact on biological processes to understand, predict, and diagnose Alzheimer’s disease.4 In addition to Alzheimer’s disease, oxysterols have also been implicated in other diseases and disorders, such as lung cancer, multiple sclerosis, and infertility.4–6

Given oxysterols’ documented role in the progression of certain diseases, researchers are using that knowledge to better understand Alzheimer’s disease as well as other diseases and disorders.

Ready to see what new insights oxysterols can help your research reveal?
Contact us today to discuss your project or study.

References

1. Anghel, Irina. “Worldwide Dementia Patients Set to Triple by 2050, Study Says.” Bloomberg. 6 January 2022. Online. 26 August 2022. https://www.bloomberg.com/news/articles/2022-01-06/worldwide-dementia-patients-set-to-triple-by-2050-study-says#xj4y7vzkg

2. Vaya, J., Schipper, H.M. Oxysterols, cholesterol homeostasis, and Alzheimer disease. Journal of Neurochemistry. 2007; 102(6): 1727-1737. https://doi.org/10.1111/j.1471-4159.2007.04689.x

3. J.R. Hascalovici, W. Song, A. Liberman, J. Vaya, S. Khatib, C. Holcroft, F. Laferla, H.M. Schipper. Neural HO-1/sterol interactions in vivo: Implications for Alzheimer’s disease. Neuroscience. 2014; 280:40-49. https://doi.org/10.1016/j.neuroscience.2014.09.001

4. Samadi A, Sabuncuoglu S, Samadi M, Isikhan SY, Chirumbolo S, Peana M, Lay I, Yalcinkaya A, Bjørklund G. A Comprehensive Review on Oxysterols and Related Diseases. Curr Med Chem. 2021; 28(1): 110-136. doi: 10.2174/0929867327666200316142659.

5. Poli G, Biasi F, Leonarduzzi G. Oxysterols in the pathogenesis of major chronic diseases. Redox Biol. 2013; 1(1):125–30.

6. Brzeska, M., Szymczyk, K., Szterk, A. Current Knowledge about Oxysterols: A Review. Journal of food science. 2016; 81: 2299-2308. DOI: https://doi.org/10.1111/1750-3841.13423

Jason Winnike, Ph.D.
Jason joined Metabolon in 2020 and is a Senior Study Director in the department of Discovery and Translational Sciences, where he serves as a scientific and technical liaison for Metabolon’s Academic, Government, and Population Health clients.

Topics

Share this article

GET STARTED

Talk with an expert

Request a quote, get detailed information on sample types, or learn how metabolomics can accelerate your research. Find our contact details are here.

Find us on:

Talk with a Metabolomics expert

References

1. Zgoda-Pols, J.R., et al., Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists. Toxicol Appl Pharmacol, 2011. 255(1): p. 48-56.

2. Bryant, J.A., et al., The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome. Nat Med, 2026. 32(1): p. 186-196

3. McGovern, B .H., et al., SER-109, an Investigational Microbiome Drugto Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial. Clin Infect Dis, 2021. 72(12): p. 2132-2140.

4. Feuerstadt, P., et al., SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med, 2022. 386(3): p. 220-229.

5. Hu, Z., et al., Targeted metabolomics reveals novel diagnostic biomarkers for colorectal cancer. Mol Oncol, 2025. 19(6): p. 1737-1750.

6. Butler, F.M., et al., Vegetarian Dietary Patterns and Diet-Related Metabolites Are Associated With Kidney Function in the Adventist Health Study-2 Cohort. J Ren Nutr, 2025.

7. Stanford, J., et al., Metabolomic Profiling and Diet Quality Scoring in a Randomized Crossover Trial of Healthy and Typical Dietary Patterns. Mol Nutr Food Res, 2025 . 69(23): p. e70271.

8. O’Connor, L.E., et al., Metabolomic Profiling of an Ultraprocessed Dietary Pattern in a Domiciled Randomized Controlled Crossover Feeding Trial. J Nutr, 2023. 153(8): p. 2181-2192.

9. Fritsch, D.A., et al., Microbiome function underpins the efficacy of a fiber-supplemented dietary intervention in dogs with chronic large bowel diarrhea. BMC Vet Res, 2022. 18(1): p. 245.

10. Leal, L.N., et al., Preweaning nutrient supply improves lactation productivity and reduces the risk of culling in Holstein cows. J Dairy Sci, 2025. 108(6): p. 5875-5888.

11. Ahsin, M., et al., Soil and pasture health underlie improved beef nutrient density determined by untargeted metabolomics in Southern US grass finished beef systems. NPJ Sci Food, 2025. 9(1): p. 151.

12. Yin, W., et al., Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia. J Lipid Res, 2012. 53(1): p. 51-65.

13. Porter, F .D., et al., Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med, 2010. 2(56): p. 56ra81.

14. Needham, B .D., et al., Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biol Psychiatry, 2021. 89(5): p. 451-462

15. Li, C., et al., Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells. J Exp Med, 2014. 211(1): p. 15-28.

16. Green, P.G., et al., Metabolic flexibility and reverse remodelling of the failing human heart. Eur Heart J, 2025. 46(25): p. 2422-2433.

17. Maekawa, H., et al., SGLT2 inhibition protects kidney function by SAM-dependent epigenetic repression of inflammatory genes under metabolic stress. J Clin Invest, 2025. 135(19).

18. Wu, D., et al., Integrated screens reveal that guanine nucleotide depletion, which is irreversible via targeting IMPDH2, inhibits pancreatic cancer and potentiates KRAS inhibition. Gut, 2026.

19. Schwerdtfeger, L.A., et al., Gut microbiota and metabolites are linked to disease progression in multiple sclerosis. Cell Rep Med, 2025. 6(4): p. 102055.

20. Wu, H., et al., Microbiome-metabolome dynamics associated with impaired glucose control and responses to lifestyle changes. Nat Med, 2025. 31(7): p. 2222-2231.

21. Jacobs, J.P., et al., Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. Microbiome, 2021. 9(1): p. 236.

22. Pietzner, M., et al., Plasma metabolites to profile pathways in noncommunicable disease multimorbidity. Nat Med, 2021. 27(3): p. 471-479.

23. Faquih, T.O., et al., Robust Metabolomic Age Prediction Based on a Wide Selection of Metabolites. J Gerontol A Biol Sci Med Sci, 2025. 80(3).

24. Scherer, N., et al., Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits. Nat Genet, 2025. 57(1): p. 193-205.

25. Holmes, Z.C., et al., Untargeted metabolomic analysis of human milk from healthy mothers reveals drivers of metabolite variability. Sci Rep, 2024. 14(1): p. 20827.

26. Titz, B., et al., Implications of Ocular Confounding Factors for Aqueous Humor Proteomic and Metabolomic Analyses in Retinal Diseases. Transl Vis Sci Technol, 2024. 13(6): p. 17.

27. Bloom, S.M., et al., Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation. Nat Microbiol, 2022. 7(3): p. 434-450.

28. Leimer, E.M., et al., Lipid profile of human synovial fluid following intra-articular ankle fracture. J Orthop Res, 2017. 35(3): p. 657-666.