Skip to main content
Springer Nature Link
Log in

Lipid Profiling in Alzheimer’s Disease

  • Conference paper
  • First Online:
GeNeDis 2022 (GeNeDis 2022)

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1423))

Abstract

The human brain is the organ with the most lipids after adipose tissues. The rich heterogeneity of the neural lipidome is being actively investigated with the aim of shedding new light into the physiological and pathological roles these compounds play in the brain. This is particularly important for the study of increasingly common neurodegenerative pathologies, such as Alzheimer’s disease (AD), whose underlying mechanisms are still insufficiently understood and for which there is no cure. The present text dives into the current knowledge of the lipid composition of the brain, with a particular focus on the application of lipid profiling to AD research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Yoon, H., Shaw, J. L., Haigis, M. C. & Greka, A. Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity. Mol. Cell 81, 3708–3730 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Fahy, E., Cotter, D., Sud, M. & Subramaniam, S. Lipid classification, structures and tools. Biochim. Biophys. Acta BBA – Mol. Cell Biol. Lipids 1811, 637–647 (2011).

    CAS  Google Scholar 

  3. Mika, A., Sledzinski, T. & Stepnowski, P. Current Progress of Lipid Analysis in Metabolic Diseases by Mass Spectrometry Methods. Curr. Med. Chem. 26, 60–103 (2019).

    CAS  PubMed  Google Scholar 

  4. Li, L. et al. Mass spectrometry methodology in lipid analysis. Int. J. Mol. Sci. 15, 10492–10507 (2014).

    PubMed  PubMed Central  Google Scholar 

  5. Wu, Z., Shon, J. C. & Liu, K.-H. Mass Spectrometry-based Lipidomics and Its Application to Biomedical Research. J. Lifestyle Med. 4, 17–33 (2014).

    PubMed  PubMed Central  Google Scholar 

  6. O’Donnell, V. B., Dennis, E. A., Wakelam, M. J. O. & Subramaniam, S. LIPID MAPS: Serving the next generation of lipid researchers with tools, resources, data, and training. Sci. Signal. 12, eaaw2964 (2019).

    PubMed  Google Scholar 

  7. Naudí, A. et al. Chapter Five – Lipidomics of Human Brain Aging and Alzheimer’s Disease Pathology. in International Review of Neurobiology (ed. Hurley, M. J.) vol. 122 133–189 (Academic Press, 2015).

    Google Scholar 

  8. Bruce, K. D., Zsombok, A. & Eckel, R. H. Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism. Front. Endocrinol. 8, (2017).

    Google Scholar 

  9. Eratne, D. et al. Alzheimer’s disease: clinical update on epidemiology, pathophysiology and diagnosis. Australas. Psychiatry Bull. R. Aust. N. Z. Coll. Psychiatr. 26, 347–357 (2018).

    Google Scholar 

  10. Lane, C. A., Hardy, J. & Schott, J. M. Alzheimer’s disease. Eur. J. Neurol. 25, 59–70 (2018).

    CAS  PubMed  Google Scholar 

  11. Scheltens, P. et al. Alzheimer’s disease. Lancet Lond. Engl. 397, 1577–1590 (2021).

    CAS  Google Scholar 

  12. Bondi, M. W., Edmonds, E. C. & Salmon, D. P. Alzheimer’s Disease: Past, Present, and Future. J. Int. Neuropsychol. Soc. JINS 23, 818–831 (2017).

    PubMed  Google Scholar 

  13. Dorszewska, J., Prendecki, M., Oczkowska, A., Dezor, M. & Kozubski, W. Molecular Basis of Familial and Sporadic Alzheimer’s Disease. Curr. Alzheimer Res. 13, 952–963 (2016).

    CAS  PubMed  Google Scholar 

  14. A Armstrong, R. Risk factors for Alzheimer’s disease. Folia Neuropathol. 57, 87–105 (2019).

    Google Scholar 

  15. Lyketsos, C. G. Treatment Development for Alzheimer’s Disease: How Are We Doing? Adv. Exp. Med. Biol. 1195, 19 (2020).

    CAS  PubMed  Google Scholar 

  16. Barupal, D. K. et al. Generation and quality control of lipidomics data for the alzheimer’s disease neuroimaging initiative cohort. Sci. Data 5, 180263 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Wilkins, J. M. & Trushina, E. Application of Metabolomics in Alzheimer’s Disease. Front. Neurol. 8, 719 (2018).

    PubMed  PubMed Central  Google Scholar 

  18. Hawrylycz, M. J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391–399 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Dawson, G. Measuring brain lipids. Biochim. Biophys. Acta 1851, 1026–1039 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Harayama, T. & Riezman, H. Understanding the diversity of membrane lipid composition. Nat. Rev. Mol. Cell Biol. 19, 281–296 (2018).

    CAS  PubMed  Google Scholar 

  21. Simons, K. & Sampaio, J. L. Membrane organization and lipid rafts. Cold Spring Harb. Perspect. Biol. 3, a004697 (2011).

    PubMed  PubMed Central  Google Scholar 

  22. O’Brien, J. S. & Sampson, E. L. Lipid composition of the normal human brain: gray matter, white matter, and myelin*. J. Lipid Res. 6, 537–544 (1965).

    PubMed  Google Scholar 

  23. Panganamala, R. V., Horrocks, L. A., Geer, J. C. & Cornwell, D. G. Positions of double bonds in the monounsaturated alk-1-enyl groups from the plasmalogens of human heart and brain. Chem. Phys. Lipids 6, 97–102 (1971).

    CAS  PubMed  Google Scholar 

  24. Kim, H.-Y., Huang, B. X. & Spector, A. A. Phosphatidylserine in the Brain: Metabolism and Function. Prog. Lipid Res. 0, 1–18 (2014).

    PubMed Central  Google Scholar 

  25. Traynor-Kaplan, A. et al. Fatty-acyl chain profiles of cellular phosphoinositides. Biochim. Biophys. Acta 1862, 513–522 (2017).

    CAS  PubMed Central  Google Scholar 

  26. Grinstein, S. Imaging signal transduction during phagocytosis: phospholipids, surface charge, and electrostatic interactions. Am. J. Physiol.-Cell Physiol. 299, C876–C881 (2010).

    CAS  PubMed  Google Scholar 

  27. Jin, U., Park, S. J. & Park, S. M. Cholesterol Metabolism in the Brain and Its Association with Parkinson’s Disease. Exp. Neurobiol. 28, 554–567 (2019).

    PubMed  PubMed Central  Google Scholar 

  28. Sezgin, E., Levental, I., Mayor, S. & Eggeling, C. The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nat. Rev. Mol. Cell Biol. 18, 361–374 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Han, X. et al. Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PloS One 6, e21643 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Hejazi, L. et al. Mass and relative elution time profiling: two-dimensional analysis of sphingolipids in Alzheimer’s disease brains. Biochem. J. 438, 165–175 (2011).

    CAS  PubMed  Google Scholar 

  31. Bazinet, R. P. & Layé, S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat. Rev. Neurosci. 15, 771–785 (2014).

    CAS  PubMed  Google Scholar 

  32. Kao, Y.-C., Ho, P.-C., Tu, Y.-K., Jou, I.-M. & Tsai, K.-J. Lipids and Alzheimer’s Disease. Int. J. Mol. Sci. 21, 1505 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Sunshine, H. & Iruela-Arispe, M. L. Membrane lipids and cell signaling. Curr. Opin. Lipidol. 28, 408–413 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Bazan, N. G. Lipid signaling in neural plasticity, brain repair, and neuroprotection. Mol. Neurobiol. 32, 89–103 (2005).

    CAS  PubMed  Google Scholar 

  35. Tassoni, D., Kaur, G., Weisinger, R. S. & Sinclair, A. J. The role of eicosanoids in the brain. Asia Pac. J. Clin. Nutr. 17 Suppl 1, 220–228 (2008).

    CAS  PubMed  Google Scholar 

  36. Mukherjee, P. K., Chawla, A., Loayza, M. S. & Bazan, N. G. Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot. Essent. Fatty Acids 77, 233–238 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Bazan, N. G. Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection. Mol. Aspects Med. 64, 18–33 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Piomelli, D., Astarita, G. & Rapaka, R. A neuroscientist’s guide to lipidomics. Nat. Rev. Neurosci. 8, 743–754 (2007).

    CAS  PubMed  Google Scholar 

  39. Tyurin, V. A. et al. Oxidative lipidomics of apoptosis: quantitative assessment of phospholipid hydroperoxides in cells and tissues. Methods Mol. Biol. Clifton NJ 610, 353–374 (2010).

    CAS  Google Scholar 

  40. Jové, M., Pradas, I., Dominguez-Gonzalez, M., Ferrer, I. & Pamplona, R. Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target. Redox Biol. 23, 101082 (2019).

    PubMed  Google Scholar 

  41. Malard, E., Valable, S., Bernaudin, M., Pérès, E. & Chatre, L. The Reactive Species Interactome in the Brain. Antioxid. Redox Signal. 35, 1176–1206 (2021).

    CAS  PubMed  Google Scholar 

  42. Pamplona, R. et al. Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets. J. Biol. Chem. 280, 21522–21530 (2005).

    CAS  PubMed  Google Scholar 

  43. Bennett, S. A. L. et al. Using neurolipidomics to identify phospholipid mediators of synaptic (dys)function in Alzheimer’s Disease. Front. Physiol. 4, 168 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Adibhatla, R. M., Hatcher, J. F. & Dempsey, R. J. Lipids and lipidomics in brain injury and diseases. AAPS J. 8, E314-321 (2006).

    PubMed  PubMed Central  Google Scholar 

  45. Cuperlovic-Culf, M. & Badhwar, A. Recent advances from metabolomics and lipidomics application in alzheimer’s disease inspiring drug discovery. Expert Opin. Drug Discov. 15, 319–331 (2020).

    CAS  PubMed  Google Scholar 

  46. Hampel, H. et al. Omics sciences for systems biology in Alzheimer’s disease: State-of-the-art of the evidence. Ageing Res. Rev. 69, 101346 (2021).

    CAS  PubMed  Google Scholar 

  47. Su, X. Q., Wang, J. & Sinclair, A. J. Plasmalogens and Alzheimer’s disease: a review. Lipids Health Dis. 18, 100 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Brosche, T. & Platt, D. The biological significance of plasmalogens in defense against oxidative damage. Exp. Gerontol. 33, 363–369 (1998).

    CAS  PubMed  Google Scholar 

  49. Martín, V. et al. Lipid alterations in lipid rafts from Alzheimer’s disease human brain cortex. J. Alzheimers Dis. JAD 19, 489–502 (2010).

    PubMed  Google Scholar 

  50. Fabelo, N. et al. Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer’s disease and facilitates APP/BACE1 interactions. Neurobiol. Aging 35, 1801–1812 (2014).

    CAS  PubMed  Google Scholar 

  51. Cheng, H., Wang, M., Li, J.-L., Cairns, N. J. & Han, X. Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer’s disease: an early event in disease pathogenesis. J. Neurochem. 127, 733–738 (2013).

    CAS  PubMed  Google Scholar 

  52. Han, X. Potential mechanisms contributing to sulfatide depletion at the earliest clinically recognizable stage of Alzheimer’s disease: a tale of shotgun lipidomics. J. Neurochem. 103 Suppl 1, 171–179 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Qiu, S. et al. Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer’s disease-like neuroinflammation and cognitive impairment. Mol. Neurodegener. 16, 64 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Cutler, R. G. et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc. Natl. Acad. Sci. U. S. A. 101, 2070–2075 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sultana, R., Perluigi, M. & Butterfield, D. A. Lipid Peroxidation Triggers Neurodegeneration: A Redox Proteomics View into the Alzheimer Disease Brain. Free Radic. Biol. Med. 62, 157–169 (2013).

    CAS  PubMed  Google Scholar 

  56. Moreira, P. I. et al. Detection and Localization of Markers of Oxidative Stress by In Situ Methods: Application in the Study of Alzheimer Disease. Methods Mol. Biol. Clifton NJ 610, 419–434 (2010).

    CAS  Google Scholar 

  57. Aldini, G., Dalle-Donne, I., Facino, R. M., Milzani, A. & Carini, M. Intervention strategies to inhibit protein carbonylation by lipoxidation-derived reactive carbonyls. Med. Res. Rev. 27, 817–868 (2007).

    CAS  PubMed  Google Scholar 

  58. Jové, M. et al. The Causal Role of Lipoxidative Damage in Mitochondrial Bioenergetic Dysfunction Linked to Alzheimer’s Disease Pathology. Life Basel Switz. 11, 388 (2021).

    Google Scholar 

  59. Chew, H., Solomon, V. A. & Fonteh, A. N. Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies. Front. Physiol. 11, 598 (2020).

    PubMed  PubMed Central  Google Scholar 

  60. Su, H. et al. Characterization of brain-derived extracellular vesicle lipids in Alzheimer’s disease. J. Extracell. Vesicles 10, e12089 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Vanherle, S., Haidar, M., Irobi, J., Bogie, J. F. J. & Hendriks, J. J. A. Extracellular vesicle-associated lipids in central nervous system disorders. Adv. Drug Deliv. Rev. 159, 322–331 (2020).

    CAS  PubMed  Google Scholar 

  62. Fuhrmann, G. Diffusion and transport of extracellular vesicles. Nat. Nanotechnol. 15, 168–169 (2020).

    CAS  PubMed  Google Scholar 

  63. Zivko, C., Fuhrmann, K., Fuhrmann, G. & Luciani, P. Tracking matricellular protein SPARC in extracellular vesicles as a non-destructive method to evaluate lipid-based antifibrotic treatments. Commun. Biol. 5, 1–13 (2022).

    Google Scholar 

  64. Zivko, C., Witt, F., Koeberle, A., Fuhrmann, G. & Luciani, P. Formulating elafibranor and obeticholic acid with phospholipids decreases drug-induced association of SPARC to extracellular vesicles from LX-2 human hepatic stellate cells. Eur. J. Pharm. Biopharm. 182, 32–40 (2023).

    CAS  PubMed  Google Scholar 

  65. Doyle, L. M. & Wang, M. Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 8, 727 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Hill, A. F. Extracellular Vesicles and Neurodegenerative Diseases. J. Neurosci. Off. J. Soc. Neurosci. 39, 9269–9273 (2019).

    Google Scholar 

  67. Machairaki, V. Human Pluripotent Stem Cells as In Vitro Models of Neurodegenerative Diseases. Adv. Exp. Med. Biol. 1195, 93–94 (2020).

    CAS  PubMed  Google Scholar 

  68. Penney, J., Ralvenius, W. T. & Tsai, L.-H. Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol. Psychiatry 25, 148–167 (2020).

    PubMed  Google Scholar 

  69. Sagar, R. et al. Biomarkers and Precision Medicine in Alzheimer’s Disease. Adv. Exp. Med. Biol. 1339, 403–408 (2021).

    CAS  PubMed  Google Scholar 

  70. Lyketsos, C. G. et al. Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimers Dement. J. Alzheimers Assoc. 7, 532–539 (2011).

    Google Scholar 

Download references

Author Contributions

Data acquisition (literature review) and conceptualization, CZ and VM; lead manuscript writing, CZ; critical revisions, RS, AX, and VM. All authors have read and agreed to the published version of the manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

 The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins Medicine, and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.

Author information

Authors and Affiliations

  1. Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Cristina Zivko, Ram Sagar, Ariadni Xydia & Vasiliki Mahairaki

  2. The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins Medicine, Baltimore, MD, USA

    Cristina Zivko, Ram Sagar, Ariadni Xydia & Vasiliki Mahairaki

Authors
  1. Cristina Zivko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ram Sagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ariadni Xydia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vasiliki Mahairaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vasiliki Mahairaki .

Editor information

Editors and Affiliations

  1. Department of Informatics, Ionian University, Corfu, Greece

    Panagiotis Vlamos

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Zivko, C., Sagar, R., Xydia, A., Mahairaki, V. (2023). Lipid Profiling in Alzheimer’s Disease. In: Vlamos, P. (eds) GeNeDis 2022. GeNeDis 2022. Advances in Experimental Medicine and Biology, vol 1423. Springer, Cham. https://doi.org/10.1007/978-3-031-31978-5_29

Download citation

Publish with us

Policies and ethics