{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:15:30Z","timestamp":1791954930498,"version":"4.3.4"},"reference-count":173,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aging induces complex changes in the lipid profiles across different areas of the brain. These changes can affect the function of brain cells and may contribute to neurodegenerative diseases such as Alzheimer\u2019s disease. Research shows that while the overall lipid profile in the human brain remains quite steady throughout adulthood, specific changes occur with age, especially after the age of 50. These changes include a slow decline in total lipid content and shifts in the composition of fatty acids, particularly in glycerophospholipids and cholesterol levels, which can vary depending on the brain region. Lipid rafts play a crucial role in maintaining membrane integrity and facilitating cellular signaling. In the context of Alzheimer\u2019s disease, changes in the composition of lipid rafts have been associated with the development of the disease. For example, alterations in lipid raft composition can lead to increased accumulation of amyloid \u03b2 (A\u03b2) peptides, contributing to neurotoxic effects. Lipid droplets store neutral lipids and are key for cellular energy metabolism. As organisms age, the dynamics of lipid droplets in the brain change, with evidence suggesting a decline in metabolic activity over time. This reduced activity may lead to an imbalance in lipid synthesis and mobilization, contributing to neurodegenerative processes. In model organisms like Drosophila, studies have shown that lipid metabolism in the brain can be influenced by diet and insulin signaling pathways, crucial for maintaining metabolic balance. The interplay between lipid metabolism, oxidative stress, and inflammation is critical in the context of aging and Alzheimer\u2019s disease. Lipid peroxidation, a consequence of oxidative stress, can lead to the formation of reactive aldehydes that further damage neurons. Inflammatory processes can also disrupt lipid metabolism, contributing to the pathology of AD. Consequently, the accumulation of oxidized lipids can affect lipid raft integrity, influencing signaling pathways involved in neuronal survival and function.<\/jats:p>","DOI":"10.3390\/biom14111362","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:15:02Z","timestamp":1730088902000},"page":"1362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Exploring the Dynamic Changes of Brain Lipids, Lipid Rafts, and Lipid Droplets in Aging and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0198-8238","authenticated-orcid":false,"given":"Michele","family":"Cerasuolo","sequence":"first","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-1454","authenticated-orcid":false,"given":"Irene","family":"Di Meo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Auriemma","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Paolisso","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6609-7453","authenticated-orcid":false,"given":"Michele","family":"Papa","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Networks Morphology and System Biology, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-4260","authenticated-orcid":false,"given":"Maria Rosaria","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_2","first-page":"860","article-title":"Membrane Rafts in Alzheimer\u2019s Disease Beta-Amyloid Production","volume":"1801","author":"Vetrivel","year":"2010","journal-title":"Biochim. Et. Biophys. Acta BBA Mol. Cell Biol. Lipids"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lee, J., and Kim, H.J. (2022). Normal Aging Induces Changes in the Brain and Neurodegeneration Progress: Review of the Structural, Biochemical, Metabolic, Cellular, and Molecular Changes. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.931536"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mesa-Herrera, F., Taoro-Gonz\u00e1lez, L., Vald\u00e9s-Baizabal, C., Diaz, M., and Mar\u00edn, R. (2019). Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153810"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.bbalip.2014.08.011","article-title":"Lipids in the Nervous System: From Biochemistry and Molecular Biology to Patho-Physiology","volume":"1851","author":"Cermenati","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23712","DOI":"10.1074\/jbc.M114.556159","article-title":"Effects of a Disrupted Blood-Brain Barrier on Cholesterol Homeostasis in the Brain","volume":"289","author":"Saeed","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/jnc.12390","article-title":"Mechanism of Cholesterol-Assisted Oligomeric Channel Formation by a Short Alzheimer \u03b2-Amyloid Peptide","volume":"128","author":"Troadec","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s11357-022-00527-1","article-title":"Selective brain regional changes in lipid profile with human aging","volume":"44","author":"Sol","year":"2022","journal-title":"Geroscience"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1146\/annurev-neuro-091922-034237","article-title":"Cholesterol Metabolism in Aging and Age-Related Disorders","volume":"46","author":"Saher","year":"2023","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.plefa.2011.04.007","article-title":"Fatty Acid Transport into the Brain: Of Fatty Acid Fables and Lipid Tails","volume":"85","author":"Mitchell","year":"2011","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_11","first-page":"735","article-title":"Fatty Acid Transport Protein Expression in Human Brain and Potential Role in Fatty Acid Transport Across Human Brain Microvessel Endothelial Cells","volume":"117","author":"Mitchell","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-P\u00e9rez, E.J., Sep\u00falveda, F.J., Peters, C., Bascu\u00f1\u00e1n, D., Riffo-Lepe, N.O., Gonz\u00e1lez-Sanmiguel, J., S\u00e1nchez, S.A., Peoples, R.W., Vicente, B., and Aguayo, L.G. (2018). Effect of Cholesterol on Membrane Fluidity and Association of A\u03b2 Oligomers and Subsequent Neuronal Damage: A Double-Edged Sword. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00226"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1051\/ocl.2011.0398","article-title":"Brain Cholesterol in Normal and Pathological Aging","volume":"18","author":"Vanmierlo","year":"2011","journal-title":"Ol\u00e9agineux Corps Gras Lipides"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3233\/JAD-2010-1242","article-title":"Lipid Alterations in Lipid Rafts from Alzheimer\u2019s Disease Human Brain Cortex","volume":"19","author":"Fabelo","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.biochi.2016.08.014","article-title":"Membrane Raft Domains and Remodeling in Aging Brain","volume":"130","author":"Colin","year":"2016","journal-title":"Biochimie"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plefa.2017.08.001","article-title":"Docosahexaenoic Acid (DHA), a Fundamental Fatty Acid for the Brain: New Dietary Sources","volume":"124","author":"Valenzuela","year":"2017","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ralhan, I., Chang, C.L., Lippincott-Schwartz, J., and Ioannou, M.S. (2021). Lipid Droplets in the Nervous System. J. Cell Biol., 220.","DOI":"10.1083\/jcb.202102136"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kao, Y.C., Ho, P.C., Tu, Y.K., Jou, I.M., and Tsai, K.J. (2020). Lipids and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041505"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Campos-Pe\u00f1a, V., Pichardo-Rojas, P., S\u00e1nchez-Barbosa, T., Ort\u00edz-Islas, E., Rodr\u00edguez-P\u00e9rez, C.E., Montes, P., Ramos-Palacios, G., Silva-Adaya, D., Valencia-Quintana, R., and Cerna-Cortes, J.F. (2022). Amyloid \u03b2, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012092"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.stem.2015.08.001","article-title":"Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer\u2019s Disease","volume":"17","author":"Hamilton","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_21","unstructured":"Ahmed, S., Shah, P., and Ahmed, O. (2024). Biochemistry, Lipids. StatPearls [Internet], StatPearls."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bbalip.2011.06.009","article-title":"Lipid classification, structures and tools","volume":"1811","author":"Fahy","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1016\/j.bbagen.2017.07.012","article-title":"Development of new ganglioside probes and unraveling of raft domain structure by single-molecule imaging","volume":"1861","author":"Suzuki","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrm.2017.16","article-title":"The mystery of membrane organization: Composition, regulation and roles of lipid rafts","volume":"18","author":"Sezgin","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Islimye, E., Girard, V., and Gould, A.P. (2022). Functions of Stress-Induced Lipid Droplets in the Nervous System. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.863907"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Farmer, B.C., Walsh, A.E., Kluemper, J.C., and Johnson, L.A. (2020). Lipid Droplets in Neurodegenerative Disorders. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00742"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s43587-024-00610-6","article-title":"A lipidome landscape of aging in mice","volume":"4","author":"Tsugawa","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrn3012","article-title":"Linking Lipids to Alzheimer\u2019s Disease: Cholesterol and Beyond","volume":"12","author":"Kim","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Szrok-Jurga, S., Turyn, J., Hebanowska, A., Swierczynski, J., Czumaj, A., Sledzinski, T., and Stelmanska, E. (2023). The Role of Acyl-CoA \u03b2-Oxidation in Brain Metabolism and Neurodegenerative Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813977"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"534","DOI":"10.2174\/1570159X14666160614091311","article-title":"Functional and Structural Benefits Induced by Omega-3 Polyunsaturated Fatty Acids During Aging","volume":"15","author":"Cutuli","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Miles, E.A., Childs, C.E., and Calder, P.C. (2021). Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review. Nutrients, 13.","DOI":"10.3390\/nu13010247"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Petrovic, S., and Arsic, A. (2016). Fatty Acids: Fatty Acids. Encycl. Food Health, 623\u2013631.","DOI":"10.1016\/B978-0-12-384947-2.00277-4"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/jcbfm.2013.128","article-title":"Why Does Brain Metabolism Not Favor Burning of Fatty Acids to Provide Energy-Reflections on Disadvantages of the Use of Free Fatty Acids as Fuel for Brain","volume":"33","author":"Reiser","year":"2013","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3233\/JAD-150336","article-title":"Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer\u2019s Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer\u2019s Disease","volume":"48","author":"Wood","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1074\/jbc.M111.274142","article-title":"Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease","volume":"287","author":"Chan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101082","DOI":"10.1016\/j.redox.2018.101082","article-title":"Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target","volume":"23","author":"Pradas","year":"2019","journal-title":"Redox Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yclnex.2018.05.001","article-title":"Lipids: An insight into the neurodegenerative disorders","volume":"20","author":"Shamim","year":"2018","journal-title":"Clin. Nutr. Exp."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12944-019-0965-z","article-title":"Role of Cholesterol and Sphingolipids in Brain Development and Neurological Diseases","volume":"18","author":"Hussain","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1016\/j.bbamcr.2013.04.010","article-title":"The complexity of sphingolipid biosynthesis in the endoplasmic reticulum","volume":"1833","author":"Tidhar","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Olsen, A.S.B., and F\u00e6rgeman, N.J. (2017). Sphingolipids: Membrane Microdomains in Brain Development, Function and Neurological Diseases. Open Biol., 7.","DOI":"10.1098\/rsob.170069"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mei, M., Liu, M., Mei, Y., Zhao, J., and Li, Y. (2023). Sphingolipid metabolism in brain insulin resistance and neurological diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1243132"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/jcp.24315","article-title":"Analysis of the Protein Network of Cholesterol Homeostasis in Different Brain Regions: An Age and Sex Dependent Perspective","volume":"228","author":"Segatto","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Korinek, M., Gonzalez-Gonzalez, I.M., Smejkalova, T., Hajdukovic, D., Skrenkova, K., Krusek, J., Horak, M., and Vyklicky, L. (2020). Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69454-5"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1194\/jlr.TR119000427","article-title":"Lipid Rafts and Neurodegeneration: Structural and Functional Roles in Physiologic Aging and Neurodegenerative Diseases","volume":"61","author":"Grassi","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1744","DOI":"10.1038\/cddis.2015.109","article-title":"Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke","volume":"6","author":"Shabanzadeh","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-Droplet-Accumulating Microglia Represent a Dysfunctional and Proinflammatory State in the Aging Brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and Functions of Lipid Droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/bs.ircmb.2017.12.007","article-title":"Lipid Droplets as Organelles","volume":"337","author":"Cohen","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1083\/jcb.201311051","article-title":"Biogenesis of the Multifunctional Lipid Droplet: Lipids, Proteins, and Sites","volume":"204","author":"Pol","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ceb.2014.03.008","article-title":"V. Lipid Droplet Biogenesis","volume":"29","author":"Wilfling","year":"2014","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.neuron.2019.10.009","article-title":"Rewiring Neuronal Glycerolipid Metabolism Determines the Extent of Axon Regeneration","volume":"105","author":"Yang","year":"2020","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14924","DOI":"10.1073\/pnas.1413706111","article-title":"The Hereditary Spastic Paraplegia-Related Enzyme DDHD2 Is a Principal Brain Triglyceride Lipase","volume":"111","author":"Inloes","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41419-018-0815-3","article-title":"Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis","volume":"9","author":"Maruyama","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1194\/jlr.M000729","article-title":"Characterization of desnutrin functional domains: Critical residues for triacylglycerol hydrolysis in cultured cells","volume":"51","author":"Duncan","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.cmet.2011.03.023","article-title":"Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase","volume":"13","author":"Ouimet","year":"2017","journal-title":"Cell Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cmet.2015.10.008","article-title":"Autophagy in the CNS and periphery coordinate lipophagy and lipolysis in the brown adipose tissue and liver","volume":"23","author":"Sahu","year":"2016","journal-title":"Cell Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41420-023-01504-z","article-title":"The regulatory role of lipophagy in central nervous system diseases","volume":"9","author":"Lan","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_58","first-page":"1178","article-title":"Breaking Fat: The Regulation and Mechanisms of Lipophagy","volume":"1862","author":"Schulze","year":"2017","journal-title":"Biochim. Et. Biophys. Acta BBA Mol. Cell Biol. Lipids"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.neurobiolaging.2015.01.002","article-title":"Human Prefrontal Cortex Phospholipids Containing Docosahexaenoic Acid Increase during Normal Adult Aging, Whereas Those Containing Arachidonic Acid Decrease","volume":"36","author":"Norris","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1007\/s11064-016-1876-2","article-title":"Looking Inside the Matrix: Perineuronal Nets in Plasticity, Maladaptive Plasticity and Neurological Disorders","volume":"41","author":"Papa","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.biotechadv.2011.05.008","article-title":"BB14, a Nerve Growth Factor (NGF)-like peptide shown to be effective in reducing reactive astrogliosis and restoring synaptic homeostasis in a rat model of peripheral nerve injury","volume":"30","author":"Cirillo","year":"2012","journal-title":"Biotechnol. Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s11745-015-4030-z","article-title":"Decreases in Phospholipids Containing Adrenic and Arachidonic Acids Occur in the Human Hippocampus over the Adult Lifespan","volume":"50","author":"Hancock","year":"2015","journal-title":"Lipids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/bs.irn.2015.05.008","article-title":"Lipidomics of human brain aging and Alzheimer\u2019s disease pathology","volume":"122","author":"Ayala","year":"2015","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_64","first-page":"52","article-title":"Chemical Biomorphosis of the Human Brain and Sciatic Nerve; a Survey","volume":"12","author":"Burger","year":"1958","journal-title":"Z. Alternsforsch."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/BF02531202","article-title":"Curvilinear Regression Course of Human Brain Lipid Composition Changes with Age","volume":"3","author":"Rouser","year":"1968","journal-title":"Lipids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1038\/s41380-018-0200-8","article-title":"Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders","volume":"25","author":"Yu","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11357-017-9961-2","article-title":"The Phospholipid Composition of the Human Entorhinal Cortex Remains Relatively Stable over 80 Years of Adult Aging","volume":"39","author":"Hancock","year":"2017","journal-title":"Geroscience"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Sarbu, M., Ica, R., and Zamfir, A.D. (2022). Gangliosides as Biomarkers of Human Brain Diseases: Trends in Discovery and Characterization by High-Performance Mass Spectrometry. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020693"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e2288","DOI":"10.1212\/WNL.0000000000207923","article-title":"Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults: A Prospective Cohort Study","volume":"101","author":"Zhou","year":"2023","journal-title":"Neurology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1037\/neu0000335","article-title":"Triglycerides are negatively correlated with cognitive function in nondemented aging adults","volume":"31","author":"Parthasarathy","year":"2017","journal-title":"Neuropsychology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kadyrov, M., Whiley, L., Brown, B., Erickson, K.I., and Holmes, E. (2022). Associations of the Lipidome with Ageing, Cognitive Decline and Exercise Behaviours. Metabolites, 12.","DOI":"10.3390\/metabo12090822"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/bs.pmbts.2018.01.009","article-title":"Gangliosides in Inflammation and Neurodegeneration","volume":"156","author":"Furukawa","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Sipione, S., Monyror, J., Galleguillos, D., Steinberg, N., and Kadam, V. (2020). Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.572965"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrendo.2013.31","article-title":"Neurosteroids as Regenerative Agents in the Brain: Therapeutic Implications","volume":"9","author":"Brinton","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2174\/1567205013666160314150017","article-title":"Lipid Raft Alterations in Aged-Associated Neuropathologies","volume":"13","author":"Marin","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neurobiolaging.2018.02.022","article-title":"\u201cLipid Raft Aging\u201d in the Human Frontal Cortex during Nonpathological Aging: Gender Influences and Potential Implications in Alzheimer\u2019s Disease","volume":"67","author":"Fabelo","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_77","first-page":"703","article-title":"Lipid Profile in Human Frontal Cortex Is Sustained Throughout Healthy Adult Life Span to Decay at Advanced Ages","volume":"73","author":"Ayala","year":"2018","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e13867","DOI":"10.1111\/acel.13867","article-title":"Molecular and biophysical features of hippocampal \u201clipid rafts aging\u201d are modified by dietary n-3 long-chain polyunsaturated fatty acids","volume":"22","author":"Santos","year":"2023","journal-title":"Aging Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/imm.12617","article-title":"Lipid rafts in immune signalling: Current progress and future perspective","volume":"149","author":"Varshney","year":"2016","journal-title":"Immunology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/MOL.0000000000000596","article-title":"Regulation of Lipid Rafts, Angiogenesis and Inflammation by AIBP HHS Public Access Author Manuscript","volume":"30","author":"Fang","year":"2019","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1016\/j.celrep.2018.04.110","article-title":"Inhibition of Neuroinflammation by AIBP: Spinal Effects upon Facilitated Pain States","volume":"23","author":"Woller","year":"2018","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12979-023-00383-3","article-title":"Toll-like receptor 4 (TLR4): New insight immune and aging","volume":"20","author":"Kim","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6978936","DOI":"10.1155\/2016\/6978936","article-title":"The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation","volume":"2016","author":"Molteni","year":"2016","journal-title":"Mediators Inflamm."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bresgen, N., Kovacs, M., Lahnsteiner, A., Felder, T.K., and Rinnerthaler, M. (2023). The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective. Biomolecules, 13.","DOI":"10.3390\/biom13060912"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10571-015-0218-2","article-title":"Astrocytes and Microglia-Mediated Immune Response in Maladaptive Plasticity Is Differently Modulated by NGF in the Ventral Horn of the Spinal Cord Following Peripheral Nerve Injury","volume":"36","author":"Savarese","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1038\/s41467-020-16358-7","article-title":"Independent regulation of age associated fat accumulation and longevity","volume":"11","author":"Beas","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/1873-3468.12902","article-title":"The role of mitochondrial ROS in the aging brain","volume":"592","author":"Stefanatos","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e2112095118","DOI":"10.1073\/pnas.2112095118","article-title":"Neuronal ROS-Induced Glial Lipid Droplet Formation Is Altered by Loss of Alzheimer\u2019s Disease-Associated Genes","volume":"118","author":"Moulton","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1007\/s10753-023-01844-z","article-title":"Pharmacological Upregulation of Microglial Lipid Droplet Alleviates Neuroinflammation and Acute Ischemic Brain Injury","volume":"46","author":"Li","year":"2023","journal-title":"Inflammation"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Kim, J., and Bai, H. (2022). Peroxisomal Stress Response and Inter-Organelle Communication in Cellular Homeostasis and Aging. Antioxidants, 11.","DOI":"10.3390\/antiox11020192"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-94-007-6889-5_3","article-title":"Aging, age-related diseases and peroxisomes","volume":"69","author":"Fransen","year":"2013","journal-title":"Subcell. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Hassan, F.U., Nadeem, A., Li, Z., Javed, M., Liu, Q., Azhar, J., Rehman, M.S., Cui, K., and Rehman, S.U. (2021). Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Energy Homeostasis of Dairy Animals: Exploiting Their Modulation through Nutrigenomic Interventions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212463"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Uzor, N.E., McCullough, L.D., and Tsvetkov, A.S. (2020). Peroxisomal Dysfunction in Neurological Diseases and Brain Aging. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00044"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/febs.16344","article-title":"Lipid Metabolism and Alzheimer\u2019s Disease: Clinical Evidence, Mechanistic Link and Therapeutic Promise","volume":"290","author":"Yin","year":"2023","journal-title":"FEBS J."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Cerasuolo, M., Papa, M., Colangelo, A.M., and Rizzo, M.R. (2023). Alzheimer\u2019s Disease from the Amyloidogenic Theory to the Puzzling Crossroads between Vascular, Metabolic and Energetic Maladaptive Plasticity. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030861"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.pneurobio.2016.01.001","article-title":"Astrogliosis: An Integral Player in the Pathogenesis of Alzheimer\u2019s Disease","volume":"144","author":"Osborn","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"108572","DOI":"10.1016\/j.celrep.2020.108572","article-title":"ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism","volume":"34","author":"Qi","year":"2021","journal-title":"Cell Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lazar, A.N., Hanbouch, L., Boussicaut, L., Fourmaux, B., Daira, P., Millan, M.J., Bernoud-Hubac, N., and Potier, M.C. (2022). Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology. Cells, 11.","DOI":"10.20944\/preprints202209.0235.v1"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2147\/CIA.S105769","article-title":"Genes associated with Alzheimer\u2019s disease: An overview and current status","volume":"11","author":"Giri","year":"2016","journal-title":"Clin. Interv. Aging"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s40001-024-01730-w","article-title":"Cortical lipid metabolic pathway alteration of early Alzheimer\u2019s disease and candidate drugs screen","volume":"29","author":"Wang","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00204-015-1517-6","article-title":"Biomarkers of lipid peroxidation in Alzheimer disease (AD): An update","volume":"89","author":"Lovell","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","article-title":"Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease","volume":"20","author":"Butterfield","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_104","first-page":"15","article-title":"Protein Oxidative Modifications: Beneficial Roles in Disease and Health","volume":"1","author":"Cai","year":"2013","journal-title":"J. Biochem. Pharmacol. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/ars.2016.6759","article-title":"The Triangle of Death in Alzheimer\u2019s Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics","volume":"26","author":"Barone","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1159\/000535131","article-title":"Brain Lipids and Lipid Droplet Dysregulation in Alzheimer\u2019s Disease and Neuropsychiatric Disorders","volume":"9","author":"Zhao","year":"2023","journal-title":"Complex. Psychiatry"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Milos, T., Rojo, D., Nedic Erjavec, G., Konjevod, M., Tudor, L., Vuic, B., Svob Strac, D., Uzun, S., Mimica, N., and Kozumplik, O. (2023). Metabolic profiling of Alzheimer\u2019s disease: Untargeted metabolomics analysis of plasma samples. Prog. Neuropsychopharmacol. Biol. Psychiatry, 127.","DOI":"10.1016\/j.pnpbp.2023.110830"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.1471-4159.2011.07498.x","article-title":"Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers","volume":"119","author":"Etschmaier","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_109","first-page":"100963","article-title":"Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: A cohort study of healthy older adults","volume":"43","author":"Hussain","year":"2023","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Miller, E., Morel, A., Saso, L., and Saluk, J. (2014). Isoprostanes and neuroprostanes as biomarkers of oxidative stress in neurodegenerative diseases. Oxidative Med. Cell. Longev., 572491.","DOI":"10.1155\/2014\/572491"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1007\/s12035-017-0689-x","article-title":"Alleviation of Neuropathology by Inhibition of Monoacylglycerol Lipase in APP Transgenic Mice Lacking CB2 Receptors","volume":"55","author":"Zhang","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12974-015-0305-9","article-title":"Monoacylglycerol Lipase Inhibitor JZL184 Reduces Neuroinflammatory Response in APdE9 Mice and in Adult Mouse Glial Cells","volume":"12","author":"Pihlaja","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Akyol, S., Ugur, Z., Yilmaz, A., Ustun, I., Gorti, S.K.K., Oh, K., McGuinness, B., Passmore, P., Kehoe, P.G., and Maddens, M.E. (2021). Lipid Profiling of Alzheimer\u2019s Disease Brain Highlights Enrichment in Glycerol(phospho)lipid, and Sphingolipid Metabolism. Cells, 10.","DOI":"10.3390\/cells10102591"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Wood, P.L., Tippireddy, S., Feriante, J., and Woltjer, R.L. (2018). Augmented frontal cortex diacylglycerol levels in Parkinson\u2019s disease and Lewy Body Disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191815"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Zheng, Q., Kebede, M.T., Kemeh, M.M., Islam, S., Lee, B., Bleck, S.D., Wurfl, L.A., and Lazo, N.D. (2019). Inhibition of the Self-Assembly of A\u03b2 and of Tau by Polyphenols: Mechanistic Studies. Molecules, 24.","DOI":"10.3390\/molecules24122316"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14740\/jocmr2815w","article-title":"Effects of N-3 Polyunsaturated Fatty Acids on Dementia","volume":"9","author":"Yanai","year":"2017","journal-title":"J. Clin. Med. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.abb.2018.12.027","article-title":"Interactions of Polyunsaturated Fatty Acids with Amyloid Peptides A\u03b240 and A\u03b242","volume":"663","author":"Pham","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Snowden, S.G., Ebshiana, A.A., Hye, A., An, Y., Pletnikova, O., O\u2019Brien, R., Troncoso, J., Legido-Quigley, C., and Thambisetty, M. (2017). Association between Fatty Acid Metabolism in the Brain and Alzheimer Disease Neuropathology and Cognitive Performance: A Nontargeted Metabolomic Study. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002266"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s40478-021-01216-4","article-title":"Age-related changes in brain phospholipids and bioactive lipids in the APP knock-in mouse model of Alzheimer\u2019s disease","volume":"9","author":"Emre","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Chew, H., Solomon, V.A., and Fonteh, A.N. (2020). Involvement of Lipids in Alzheimer\u2019s Disease Pathology and Potential Therapies. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00598"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/med.21597","article-title":"Lipoprotein-associated phospholipase A2: The story continues","volume":"40","author":"Huang","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Watanabe, Y., Kasuga, K., Tokutake, T., Kitamura, K., Ikeuchi, T., and Nakamura, K. (2021). Alterations in Glycerolipid and Fatty Acid Metabolic Pathways in Alzheimer\u2019s Disease Identified by Urinary Metabolic Profiling: A Pilot Study. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.719159"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"148197","DOI":"10.1016\/j.brainres.2022.148197","article-title":"Analysis of the time-dependent changes of phospholipids in the brain regions of a mouse model of Alzheimer\u2019s disease","volume":"1800","author":"Omori","year":"2023","journal-title":"Brain Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3390\/ijms14011310","article-title":"Phospholipids and Alzheimer\u2019s disease: Alterations, mechanisms and potential biomarkers","volume":"14","author":"Kosicek","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"de Wit, N.M., Mol, K., Rodr\u00edguez-Lorenzo, S., de Vries, H.E., and Kooij, G. (2021). The Role of Sphingolipids and Specialized Pro-Resolving Mediators in Alzheimer\u2019s Disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.620348"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8653","DOI":"10.1523\/JNEUROSCI.1429-16.2016","article-title":"Neutral Sphingomyelinase-2 Deficiency Ameliorates Alzheimer\u2019s Disease Pathology and Improves Cognition in the 5XFAD Mouse","volume":"36","author":"Dinkins","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.expneurol.2018.09.012","article-title":"Inhibition of Sphingomyelin Synthase 1 Ameliorates Alzheimer-like Pathology in APP\/PS1 Transgenic Mice through Promoting Lysosomal Degradation of BACE1","volume":"311","author":"Lu","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Wirths, O., Walter, J., Saher, G., Don, A., Nordstr\u00f6m, V., Herzer, S., Hagan, C., Von Gerichten, J., Dieterle, V., and Munteanu, B. (2018). Deletion of Specific Sphingolipids in Distinct Neurons Improves Spatial Memory in a Mouse Model of Alzheimer\u2019s Disease. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00206"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.bbalip.2010.01.010","article-title":"Multi-dimensional mass spectrometry-based shotgun lipidomics and the altered lipids at the mild cognitive impairment stage of Alzheimer\u2019s disease","volume":"1801","author":"Han","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13024-021-00488-7","article-title":"Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer\u2019s disease-like neuroinflammation and cognitive impairment","volume":"16","author":"Qiu","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3233\/JAD-160925","article-title":"The Association Between Plasma Ceramides and Sphingomyelins and Risk of Alzheimer\u2019s Disease Differs by Sex and APOE in the Baltimore Longitudinal Study of Aging","volume":"60","author":"Mielke","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"586","DOI":"10.2174\/1567205014666170117094038","article-title":"Brain Gangliosides in Alzheimer\u2019s Disease: Increased Expression of Cholinergic Neuron-Specific Gangliosides","volume":"14","author":"Fukami","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jsbmb.2019.03.003","article-title":"Alterations in cholesterol metabolism as a risk factor for developing Alzheimer\u2019s disease: Potential novel targets for treatment","volume":"190","author":"Goikolea","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41514-021-00064-9","article-title":"Abnormal brain cholesterol homeostasis in Alzheimer\u2019s disease\u2014A targeted metabolomic and transcriptomic study","volume":"7","author":"Varma","year":"2021","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Rudajev, V., and Novotny, J. (2023). Cholesterol-Dependent Amyloid \u03b2 Production: Space for Multifarious Interactions between Amyloid Precursor Protein, Secretases, and Cholesterol. Cell Biosci., 13.","DOI":"10.1186\/s13578-023-01127-y"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s13195-023-01342-2","article-title":"Distinct effects of cholesterol profile components on amyloid and vascular burdens","volume":"15","author":"Kang","year":"2023","journal-title":"Alzheimers Res. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Marwarha, G., Raza, S., Prasanthi, J.R.P., and Ghribi, O. (2013). Gadd153 and NF-KB Crosstalk Regulates 27-Hydroxycholesterol-Induced Increase in BACE1 and \u03b2-Amyloid Production in Human Neuroblastoma SH-SY5Y Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070773"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Han, X., Rozen, S., Boyle, S.H., Hellegers, C., Cheng, H., Burke, J.R., Welsh-Bohmer, K.A., Doraiswamy, P.M., and Kaddurah-Daouk, R. (2011). Metabolomics in early Alzheimer\u2019s disease: Identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021643"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3233\/JAD-160169","article-title":"Alzheimer\u2019s Disease Risk Genes and Lipid Regulators","volume":"53","author":"Jing","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.brainresbull.2010.02.013","article-title":"Lipid Rafts: Keys to Neurodegeneration","volume":"82","author":"Schengrund","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_141","first-page":"1185","article-title":"Biophysical Alterations in Lipid Rafts from Human Cerebral Cortex Associate with Increased BACE1\/A\u03b2PP Interaction in Early Stages of Alzheimer\u2019s Disease","volume":"43","author":"Fabelo","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1021\/acschemneuro.2c00221","article-title":"Monosialotetrahexosylganglioside Promotes Early A\u03b242 Oligomer Formation and Maintenance","volume":"13","author":"Zhang","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Cascella, R., and Cecchi, C. (2021). Calcium Dyshomeostasis in Alzheimer\u2019s Disease Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094914"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Deng, C., Barr, A., Rojo, L.E., Gaspar, P.A., Castillo, R.I., Henriquez-Henriquez, M., Silva, H., Maturana, A., Villar, M.J., and Fuentes, M. (2016). From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism. Front. Neurosci., 10.","DOI":"10.3389\/fnins.2016.00488"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/jnc.13589","article-title":"The Role of Sphingolipids in Neuronal Plasticity of the Brain","volume":"137","author":"Sonnino","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S1474-4422(15)00050-2","article-title":"Neuroimaging in Autism Spectrum Disorder: Brain Structure and Function across the Lifespan","volume":"14","author":"Ecker","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Hussain, G., Schmitt, F., Loeffler, J.P., and de Aguilar, J.L.G. (2013). Fatting the Brain: A Brief of Recent Research. Front. Cell. Neurosci., 7.","DOI":"10.3389\/fncel.2013.00144"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cmet.2017.08.024","article-title":"The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE\/D","volume":"26","author":"Liu","year":"2017","journal-title":"Cell Metab."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.1073\/pnas.1705080114","article-title":"A Mechanism for Lipid Binding to ApoE and the Role of Intrinsically Disordered Regions Coupled to Domain-Domain Interactions","volume":"114","author":"Frieden","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer Disease: Risk, Mechanisms and Therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Ioannou, M.S., Liu, Z., and Lippincott-Schwartz, J. (2019). A Neuron-Glia Co-Culture System for Studying Intercellular Lipid Transport. Curr. Protoc. Cell Biol., 84.","DOI":"10.1002\/cpcb.95"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cell.2014.12.019","article-title":"Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration","volume":"160","author":"Liu","year":"2015","journal-title":"Cell"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Victor, M.B., Leary, N., Luna, X., Meharena, H.S., Scannail, A.N., Bozzelli, P.L., Samaan, G., Murdock, M.H., von Maydell, D., and Effenberger, A.H. (Cell Stem Cell, 1197). Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity, Cell Stem Cell.","DOI":"10.1016\/j.stem.2022.07.005"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"108224","DOI":"10.1016\/j.celrep.2020.108224","article-title":"PICALM Rescues Endocytic Defects Caused by the Alzheimer\u2019s Disease Risk Factor APOE4","volume":"33","author":"Narayan","year":"2020","journal-title":"Cell Rep."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Nuriel, T., Peng, K.Y., Ashok, A., Dillman, A.A., Figueroa, H.Y., Apuzzo, J., Ambat, J., Levy, E., Cookson, M.R., and Mathews, P.M. (2017). The Endosomal-Lysosomal Pathway Is Dysregulated by APOE4 Expression In Vivo. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00702"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-024-07185-7","article-title":"APOE4\/4 is linked to damaging lipid droplets in Alzheimer\u2019s disease microglia","volume":"628","author":"Haney","year":"2024","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbamcr.2015.12.005","article-title":"Peroxisomes in brain development and function","volume":"1863","author":"Berger","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1007\/s12640-020-00323-9","article-title":"Peroxisomes of the Brain: Distribution, Functions, and Associated Diseases","volume":"39","author":"Deb","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00702-017-1699-6","article-title":"Differential Diagnosis between Patients with Probable Alzheimer\u2019s Disease, Parkinson\u2019s Disease Dementia, or Dementia with Lewy Bodies and Frontotemporal Dementia, Behavioral Variant, Using Quantitative Electroencephalographic Features","volume":"124","author":"Garn","year":"2017","journal-title":"J. Neural Transm."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a Biological Definition of Alzheimer\u2019s Disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"fcac134","DOI":"10.1093\/braincomms\/fcac134","article-title":"Brain Alterations in the Early Alzheimer\u2019s Continuum with Amyloid-\u03b2, Tau, Glial and Neurodegeneration CSF Markers","volume":"4","author":"Shekari","year":"2022","journal-title":"Brain Commun."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Barcel\u00f3-Coblijn, G., D\u00edaz, M., and Catal\u00e1, A. (2016). Editorial: Impact of Lipid Peroxidation on the Physiology and Pathophysiology of Cell Membranes. Front. Physiol., 7.","DOI":"10.3389\/fphys.2016.00423"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.redox.2016.09.001","article-title":"Changes in Brain Oxysterols at Different Stages of Alzheimer\u2019s Disease: Their Involvement in Neuroinflammation","volume":"10","author":"Testa","year":"2016","journal-title":"Redox Biol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Ito, F., Sono, Y., and Ito, T. (2019). Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation. Antioxidants, 8.","DOI":"10.3390\/antiox8030072"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2016.02.030","article-title":"Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer\u2019s disease pathology","volume":"42","author":"Scheff","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Ros\u00e9n, C., Mattsson, N., Johansson, P.M., Andreasson, U., Wallin, A., Hansson, O., Johansson, J.O., Lamont, J., Svensson, J., and Blennow, K. (2011). Discriminatory Analysis of Biochip-Derived Protein Patterns in CSF and Plasma in Neurodegenerative Diseases. Front. Aging Neurosci., 3.","DOI":"10.3389\/fnagi.2011.00001"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2217\/fnl-2018-0003","article-title":"Role of FABP3 as Biomarker in Alzheimer\u2019s Disease and Synucleinopathies","volume":"13","author":"Sepe","year":"2018","journal-title":"Future Neurol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.3233\/JAD-2010-101293","article-title":"CSF Levels of Heart Fatty Acid Binding Protein Are Altered During Early Phases of Alzheimer\u2019s Disease","volume":"22","author":"Chiasserini","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.biopsych.2013.11.032","article-title":"Phosphorylated Tau-A\u03b242 Ratio as a Continuous Trait for Biomarker Discovery for Early-Stage Alzheimer\u2019s Disease in Multiplex Immunoassay Panels of Cerebrospinal Fluid","volume":"75","author":"Harari","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Conte, M., Medici, V., Malagoli, D., Chiariello, A., Cirrincione, A., Davin, A., Chikhladze, M., Vasuri, F., Legname, G., and Ferrer, I. (2022). Expression Pattern of Perilipins in Human Brain during Aging and in Alzheimer\u2019s Disease. Neuropathol. Appl. Neurobiol., 48.","DOI":"10.1111\/nan.12756"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13195-023-01162-4","article-title":"Molecular insights into sex-specific metabolic alterations in Alzheimer\u2019s mouse brain using multi-omics approach","volume":"15","author":"Strefeler","year":"2023","journal-title":"Alzheimer Res. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s41398-021-01362-2","article-title":"Plasma lipidome is dysregulated in Alzheimer\u2019s disease and is associated with disease risk genes","volume":"11","author":"Liu","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-3-030-32633-3_14","article-title":"Nutritional Lipidomics in Alzheimer\u2019s Disease","volume":"1195","author":"Kalli","year":"2020","journal-title":"Adv. Exp. Med. Biol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/11\/1362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:21:10Z","timestamp":1760113270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/11\/1362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,26]]},"references-count":173,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["biom14111362"],"URL":"https:\/\/doi.org\/10.3390\/biom14111362","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,26]]}}}