{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:47:55Z","timestamp":1790185675104,"version":"4.1.0"},"reference-count":126,"publisher":"IMR Press","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a multifactorial neurodegenerative disease that is conventionally characterized by amyloid-\u03b2 and tau pathology. There is growing evidence, however, that lipid metabolic disturbances are part of the biology of the disease, and not a secondary phenomenon. Lipid signaling controls membrane organization, amyloid precursor protein, tau phosphorylation, mitochondrial energetics, neuroinflammatory signaling, and synaptic stability. The accumulating genetic evidence, including risk variants in the APOE (apolipoprotein E), ABCA1 (ATP-binding cassette subfamily A member 1), ABCA7 (ATP-binding cassette subfamily A member 7), and TREM2 (Triggering receptor expressed on myeloid cells 2) genes, further makes lipid transport and lipid-sensing pathways central to late-onset AD vulnerability. Recent developments in lipidomics based on mass spectrometry have revealed concerted changes in phospholipids, sphingolipids, sterols, and oxidized lipid derivatives in brain tissue and peripheral biofluids. Instead of single abnormalities, directional metabolic imbalance is indicated by pathway changes, including decreased sphingomyelin-to-ceramide ratios and decreased polyunsaturated phospholipids. Co-analysis of lipidomic, genomic, and proteomic data has shown the existence of metabolically different subgroups, which aids genotype stratified risk evaluation and the lipid responder phenotype concept. Protein-centered therapies are complemented by therapeutic strategies that focus on lipid homeostasis, such as the regulation of cholesterol efflux, sphingolipid metabolism, pro-resolving lipid mediators, and metabolic reprogramming. There is also emerging evidence that implicates peroxisomal dysfunction and compromised glymphatic clearance in interfering with lipid balance. Although this field of research has come a long way, the issues of proving causality, standardizing lipidomic techniques, and converting pathway signatures into clinically useful resources persist. Restructuring AD as a lipid network instability disorder offers a systems level model of earlier diagnosis and targeted treatment.<\/jats:p>","DOI":"10.31083\/jin48436","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:26:43Z","timestamp":1777451203000},"source":"Crossref","is-referenced-by-count":3,"title":["Targeting Lipid Metabolism in Alzheimer\u2019s Disease: Emerging Insights and Future Directions"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7543-8435","authenticated-orcid":true,"given":"Jeyakumar","family":"Balakrishnan","sequence":"first","affiliation":[{"name":"Central Research Laboratory for Biomedical Research, Vinayaka Mission\u2019s Medical College and Hospital, Vinayaka Mission Research Foundation (A unit of VMRF-DU), 609609 Karaikal, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-7405","authenticated-orcid":true,"given":"Suganya","family":"Kannan","sequence":"additional","affiliation":[{"name":"Central Research Laboratory for Biomedical Research, Vinayaka Mission\u2019s Medical College and Hospital, Vinayaka Mission Research Foundation (A unit of VMRF-DU), 609609 Karaikal, Puducherry, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-8343","authenticated-orcid":true,"given":"Kathiresan","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Integrative Biology, Central University of Tamil Nadu, 610005 Thiruvarur, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9077-9940","authenticated-orcid":true,"given":"Dhavamani","family":"Sugasini","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Illinois, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Grobler C, van Tongeren M, Gettemans J, Kell DB, Pretorius E. Alzheimer\u2019s Disease: A Systems View Provides a Unifying Explanation of Its Development. Journal of Alzheimer\u2019s Disease. 2023; 91: 43\u201370.","DOI":"10.3233\/JAD-220720"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Molecular Medicine. 2016; 8: 595\u2013608.","DOI":"10.15252\/emmm.201606210"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"De Strooper B, Karran E. The Cellular Phase of Alzheimer\u2019s Disease. Cell. 2016; 164: 603\u2013615.","DOI":"10.1016\/j.cell.2015.12.056"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"de Oliveira J, Kucharska E, Garcez ML, Rodrigues MS, Quevedo J, Moreno-Gonzalez I, et al. Inflammatory Cascade in Alzheimer\u2019s Disease Pathogenesis: A Review of Experimental Findings. Cells. 2021; 10: 2581.","DOI":"10.3390\/cells10102581"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Cummings J, Lee G, Zhong K, Fonseca J, Taghva K. Alzheimer\u2019s disease drug development pipeline: 2021. Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions. 2021; 7: e12179.","DOI":"10.1002\/trc2.12179"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Knopman DS, Amieva H, Petersen RC, Ch\u00e9telat G, Holtzman DM, Hyman BT, et al. Alzheimer disease. Nature Reviews. Disease Primers. 2021; 7: 33.","DOI":"10.1038\/s41572-021-00269-y"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer\u2019s disease drug development pipeline: 2023. Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions. 2023; 9: e12385.","DOI":"10.1002\/trc2.12385"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Di Paolo G, Kim TW. Linking lipids to Alzheimer\u2019s disease: cholesterol and beyond. Nature Reviews. Neuroscience. 2011; 12: 284\u2013296.","DOI":"10.1038\/nrn3012"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Chew H, Solomon VA, Fonteh AN. Involvement of Lipids in Alzheimer\u2019s Disease Pathology and Potential Therapies. Frontiers in Physiology. 2020; 11: 598.","DOI":"10.3389\/fphys.2020.00598"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Han YH, Liu XD, Jin MH, Sun HN, Kwon T. Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases. Inflammation Research. 2023; 72: 1839\u20131859.","DOI":"10.1007\/s00011-023-01790-4"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"O\u2019Brien JS, Sampson EL. Lipid composition of the normal human brain: gray matter, white matter, and myelin. Journal of Lipid Research. 1965; 6: 537\u2013544.","DOI":"10.1016\/S0022-2275(20)39619-X"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Bazan NG. Brain self-protection by bioactive lipids. Brain Aging and Resilience: Exploring the Adaptability of the Human Brain in the Face of Aging and Adverse Conditions (pp. 139\u2013174). Springer Nature Switzerland: Cham. 2025.","DOI":"10.1007\/978-3-031-94431-4_11"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Puglielli L, Tanzi RE, Kovacs DM. Alzheimer\u2019s disease: the cholesterol connection. Nature Neuroscience. 2003; 6: 345\u2013351.","DOI":"10.1038\/nn0403-345"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1993; 90: 1977\u20131981.","DOI":"10.1073\/pnas.90.5.1977"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nature Reviews. Neurology. 2013; 9: 106\u2013118.","DOI":"10.1038\/nrneurol.2012.263"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Mahley RW, Huang Y. Apolipoprotein E: from atherosclerosis to Alzheimer\u2019s disease and beyond. Current Opinion in Lipidology. 1999; 10: 207\u2013217.","DOI":"10.1097\/00041433-199906000-00003"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, et al. Human apoE isoforms differentially regulate brain amyloid-\u03b2 peptide clearance. Science Translational Medicine. 2011; 3: 89ra57.","DOI":"10.1126\/scitranslmed.3002156"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Yamazaki Y, Liu CC, Yamazaki A, Shue F, Martens YA, Chen Y, et al. Vascular ApoE4 Impairs Behavior by Modulating Gliovascular Function. Neuron. 2021; 109: 438\u2013447.e6.","DOI":"10.1016\/j.neuron.2020.11.019"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Giridharan VV, Masud F, Petronilho F, Dal-Pizzol F, Barichello T. Infection-Induced Systemic Inflammation Is a Potential Driver of Alzheimer\u2019s Disease Progression. Frontiers in Aging Neuroscience. 2019; 11: 122.","DOI":"10.3389\/fnagi.2019.00122"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Han X, M Holtzman D, McKeel DW Jr, Kelley J, Morris JC. Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer\u2019s disease: potential role in disease pathogenesis. Journal of Neurochemistry. 2002; 82: 809\u2013818.","DOI":"10.1046\/j.1471-4159.2002.00997.x"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Yin F. Lipid metabolism and Alzheimer\u2019s disease: clinical evidence, mechanistic link and therapeutic promise. The FEBS Journal. 2023; 290: 1420\u20131453.","DOI":"10.1111\/febs.16344"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Gonz\u00e1lez-Dom\u00ednguez R, Gonz\u00e1lez-Dom\u00ednguez \u00c1, Sayago A, Fern\u00e1ndez-Recamales \u00c1. Mass spectrometry-based metabolomic multiplatform for Alzheimer\u2019s disease research. In Perneczky R (ed.) Biomarkers for Alzheimer\u2019s Disease Drug Development (pp. 125\u2013137). Springer: New York. 2018.","DOI":"10.1007\/978-1-4939-7704-8_8"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and \u2018wingmen\u2019. Nature Neuroscience. 2015; 18: 800\u2013806.","DOI":"10.1038\/nn.4018"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Snyder PJ, Alber J, Alt C, Bain LJ, Bouma BE, Bouwman FH, et al. Retinal imaging in Alzheimer\u2019s and neurodegenerative diseases. Alzheimer\u2019s & Dementia. 2021; 17: 103\u2013111.","DOI":"10.1002\/alz.12179"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Ehehalt R, Keller P, Haass C, Thiele C, Simons K. Amyloidogenic processing of the Alzheimer \u03b2-amyloid precursor protein depends on lipid rafts. The Journal of Cell Biology. 2003; 160: 113\u2013123.","DOI":"10.1083\/jcb.200207113"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of \u03b2-amyloid in hippocampal neurons. Proceedings of the National Academy of Sciences of the United States of America. 1998; 95: 6460\u20136464.","DOI":"10.1073\/pnas.95.11.6460"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Yanagisawa K, Odaka A, Suzuki N, Ihara Y. GM1 ganglioside-bound amyloid \u03b2-protein (A\u03b2): a possible form of preamyloid in Alzheimer\u2019s disease. Nature Medicine. 1995; 1: 1062\u20131066.","DOI":"10.1038\/nm1095-1062"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"H\u00e4llqvist J, Taanman JW, G\u00f6teson A, Heywood WE, Schott JM, Hardy J, et al. Plasmalogen deficiency and the Alzheimer\u2019s disease risk of apolipoprotein E4. Brain Communications. 2026; 8: fcag040.","DOI":"10.1093\/braincomms\/fcag040"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Gonz\u00e1lez-Dom\u00ednguez R, Castellano-Escuder P, Lef\u00e8vre-Arbogast S, Low DY, Du Preez A, Ruigrok SR, et al. Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline. Alzheimer\u2019s Research & Therapy. 2022; 14: 1.","DOI":"10.1186\/s13195-021-00948-8"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Trushina E, Trushin S, Hasan MF. Mitochondrial complex I as a therapeutic target for Alzheimer\u2019s disease. Acta Pharmaceutica Sinica. B. 2022; 12: 483\u2013495.","DOI":"10.1016\/j.apsb.2021.11.003"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Liu C, Liu J, Wang YY, Xu SF, Yu LM. APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer\u2019s Disease and Cardiovascular Disease. Molecular Neurobiology. 2026; 63: 325\u2013344.","DOI":"10.1007\/s12035-025-05629-3"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Petrov AM, Mast N, Li Y, Denker J, Pikuleva IA. Brain sterol flux mediated by cytochrome P450 46A1 affects membrane properties and membrane-dependent processes. Brain Communications. 2020; 2: fcaa043.","DOI":"10.1093\/braincomms\/fcaa043"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nature Reviews. Drug Discovery. 2020; 19: 609\u2013633.","DOI":"10.1038\/s41573-020-0072-x"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Sugasini D, Park JC, McAnany JJ, Kim TH, Ma G, Yao X, et al. Improvement of retinal function in Alzheimer disease-associated retinopathy by dietary lysophosphatidylcholine-EPA\/DHA. Scientific Reports. 2023; 13: 9179.","DOI":"10.1038\/s41598-023-36268-0"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Balakrishnan J, Dhavamani S, Sadasivam SG, Arumugam M, Vellaikumar S, Ramalingam J, et al. Omega-3-rich Isochrysis sp. biomass enhances brain docosahexaenoic acid levels and improves serum lipid profile and antioxidant status in Wistar rats. Journal of the Science of Food and Agriculture. 2019; 99: 6066\u20136075.","DOI":"10.1002\/jsfa.9884"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nature Reviews. Molecular Cell Biology. 2008; 9: 112\u2013124.","DOI":"10.1038\/nrm2330"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Almsherqi ZA. Potential Role of Plasmalogens in the Modulation of Biomembrane Morphology. Frontiers in Cell and Developmental Biology. 2021; 9: 673917.","DOI":"10.3389\/fcell.2021.673917"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Haughey NJ, Bandaru VVR, Bae M, Mattson MP. Roles for dysfunctional sphingolipid metabolism in Alzheimer\u2019s disease neuropathogenesis. Biochimica et Biophysica Acta. 2010; 1801: 878\u2013886.","DOI":"10.1016\/j.bbalip.2010.05.003"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Dietschy JM, Turley SD. Cholesterol metabolism in the central nervous system during early development and in the mature animal. Journal of Lipid Research. 2001; 45: 1375\u201397.","DOI":"10.1194\/jlr.R400004-JLR200"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Salem N Jr, Litman B, Kim HY, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001; 36: 945\u2013959.","DOI":"10.1007\/s11745-001-0805-6"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Barber CN, Raben DM. Lipid Metabolism Crosstalk in the Brain: Glia and Neurons. Frontiers in Cellular Neuroscience. 2019; 13: 212.","DOI":"10.3389\/fncel.2019.00212"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Alaamery M, Albesher N, Aljawini N, Alsuwailm M, Massadeh S, Wheeler MA, et al. Role of sphingolipid metabolism in neurodegeneration. Journal of Neurochemistry. 2021; 158: 25\u201335.","DOI":"10.1111\/jnc.15044"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. The Journal of Biological Chemistry. 1986; 261: 6084\u20136089.","DOI":"10.1016\/S0021-9258(17)38495-8"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Markesbery WR, Lovell MA. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer\u2019s disease. Neurobiology of Aging. 1998; 19: 33\u201336.","DOI":"10.1016\/s0197-4580(98)00009-8"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Falabella M, Vernon HJ, Hanna MG, Claypool SM, Pitceathly RD. Cardiolipin, mitochondria, and neurological disease. Trends in Endocrinology & Metabolism. 2021; 32: 224-37.","DOI":"10.1016\/j.tem.2021.01.006"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Goodenowe DB, Haroon J, Kling MA, Zielinski M, Mahdavi K, Habelhah B, et al. Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons. Frontiers in Cell and Developmental Biology. 2022; 10: 864842.","DOI":"10.3389\/fcell.2022.864842"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Hou J, Chen Y, Grajales-Reyes G, Colonna M. TREM2 dependent and independent functions of microglia in Alzheimer\u2019s disease. Molecular Neurodegeneration. 2022; 17: 84.","DOI":"10.1186\/s13024-022-00588-y"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Marizzoni M, Coppola L, Festari C, Luongo D, Salamone D, Naviglio D, et al. Circulating short chain fatty acids in Alzheimer\u2019s disease: A cross-sectional observational study. Journal of Alzheimer\u2019s Disease. 2025; 106: 38\u201343.","DOI":"10.1177\/13872877251337773"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Badesso S, Cartas-Cejudo P, Espelosin M, Santamaria E, Cuadrado-Tejedor M, Garcia-Osta A. Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer\u2019s Disease Mouse Model: Cellular and Molecular Correlates. Pharmaceutics. 2022; 15: 82.","DOI":"10.3390\/pharmaceutics15010082"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Su XQ, Wang J, Sinclair AJ. Plasmalogens and Alzheimer\u2019s disease: a review. Lipids in Health and Disease. 2019; 18: 100.","DOI":"10.1186\/s12944-019-1044-1"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Mielke MM, Haughey NJ, Han D, An Y, Bandaru VVR, Lyketsos CG, et al. 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. Journal of Alzheimer\u2019s Disease. 2017; 60: 819\u2013828.","DOI":"10.3233\/JAD-160925"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Cunnane SC, Plourde M, Pifferi F, B\u00e9gin M, F\u00e9art C, Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer\u2019s disease. Progress in Lipid Research. 2009; 48: 239\u2013256.","DOI":"10.1016\/j.plipres.2009.04.001"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Hui L, Soliman ML, Geiger NH, Miller NM, Afghah Z, Lakpa KL, et al. Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis. Journal of Alzheimer\u2019s Disease. 2019; 67: 393\u2013410.","DOI":"10.3233\/JAD-180941"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Paseban T, Alavi MS, Etemad L, Roohbakhsh A. The role of the ATP-Binding Cassette A1 (ABCA1) in neurological disorders: a mechanistic review. Expert Opinion on Therapeutic Targets. 2023; 27: 531\u2013552.","DOI":"10.1080\/14728222.2023.2235718"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, et al. Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity. Cell. 2019; 177: 1522\u20131535.e14.","DOI":"10.1016\/j.cell.2019.04.001"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proceedings of the National Academy of Sciences of the United States of America. 1999; 96: 7238\u20137243.","DOI":"10.1073\/pnas.96.13.7238"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Schumacher MM, DeBose-Boyd RA. Posttranslational Regulation of HMG CoA Reductase, the Rate-Limiting Enzyme in Synthesis of Cholesterol. Annual Review of Biochemistry. 2021; 90: 659\u2013679.","DOI":"10.1146\/annurev-biochem-081820-101010"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Li Z, Zheng D, Zhang T, Ruan S, Li N, Yu Y, et al. The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease. Hepatology Communications. 2024; 8: e0343.","DOI":"10.1097\/HC9.0000000000000343"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Egawa J, Pearn ML, Lemkuil BP, Patel PM, Head BP. Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function. The Journal of Physiology. 2016; 594: 4565\u20134579.","DOI":"10.1113\/JP270590"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Chausse B, Kakimoto PA, Kann O. Microglia and lipids: how metabolism controls brain innate immunity. Seminars in Cell & Developmental Biology. 2021; 112: 137\u2013144.","DOI":"10.1016\/j.semcdb.2020.08.001"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Barnes-V\u00e9lez JA, Aksoy Yasar FB, Hu J. Myelin lipid metabolism and its role in myelination and myelin maintenance. The Innovation. 2023; 4: 100360.","DOI":"10.1016\/j.xinn.2022.100360"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"He X, Huang Y, Li B, Gong CX, Schuchman EH. Deregulation of sphingolipid metabolism in Alzheimer\u2019s disease. Neurobiology of Aging. 2010; 31: 398\u2013408.","DOI":"10.1016\/j.neurobiolaging.2008.05.010"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Belayev L, Hong SH, Menghani H, Marcell SJ, Obenaus A, Freitas RS, et al. Docosanoids promote neurogenesis and angiogenesis, blood-brain barrier integrity, penumbra protection, and neurobehavioral recovery after experimental ischemic stroke. Molecular Neurobiology. 2018; 55: 7090-7106.","DOI":"10.1007\/s12035-018-1136-3"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer\u2019s disease. The Lancet. Neurology. 2015; 14: 388\u2013405.","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"L\u00f3pez-Vicario C, Rius B, Alcaraz-Quiles J, Garc\u00eda-Alonso V, Lopategi A, Titos E, et al. Pro-resolving mediators produced from EPA and DHA: Overview of the pathways involved and their mechanisms in metabolic syndrome and related liver diseases. European Journal of Pharmacology. 2016; 785: 133\u2013143.","DOI":"10.1016\/j.ejphar.2015.03.092"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Stephenson RA, Sepulveda J, Johnson KR, Lita A, Gopalakrishnan J, Acri DJ, et al. Triglyceride metabolism controls inflammation and microglial phenotypes associated with APOE4. Cell reports. 2025; 22: 44.","DOI":"10.1016\/j.celrep.2025.115961"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Jo SL, Hong EJ. Progesterone Receptor Membrane Component 1 Regulates Cellular Stress Responses and Inflammatory Pathways in Chronic Neuroinflammatory Conditions. Antioxidants. 2024; 13: 230.","DOI":"10.3390\/antiox13020230"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer\u2019s disease: synapse loss is the major correlate of cognitive impairment. Annals of Neurology. 1991; 30: 572\u2013580.","DOI":"10.1002\/ana.410300410"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"Cruz JN, Magro DD, Lima DD, Cruz JG. Simvastatin treatment reduces the cholesterol content of membrane\/lipid rafts, implicating the N-methyl-D-aspartate receptor in anxiety: a literature review. Brazilian Journal of Pharmaceutical Sciences. 2017; 53: e16102.","DOI":"10.1590\/s2175-97902017000116102"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"Behl T, Kaur I, Sehgal A, Kumar A, Uddin MS, Bungau S. The interplay of ABC transporters in A\u03b2 translocation and cholesterol metabolism: implicating their roles in Alzheimer\u2019s disease. Molecular Neurobiology. 2021; 58: 1564\u20131582.","DOI":"10.1007\/s12035-020-02211-x"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"van Echten-Deckert G. The role of sphingosine 1-phosphate metabolism in brain health and disease. Pharmacology & Therapeutics. 2023; 244: 108381.","DOI":"10.1016\/j.pharmthera.2023.108381"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"Ferreira HB, Domingues MR. Oxidized phospholipid-protein adducts: The future targets of interest. Archives of Biochemistry and Biophysics. 2024; 754: 109956.","DOI":"10.1016\/j.abb.2024.109956"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"Sural-Fehr T, Bongarzone ER. How membrane dysfunction influences neuronal survival pathways in sphingolipid storage disorders. Journal of Neuroscience Research. 2016; 94: 1042\u20131048.","DOI":"10.1002\/jnr.23763"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"Silva A, Prior R, D\u2019Antonio M, Swinnen JV, Van Den Bosch L. Lipid metabolism alterations in peripheral neuropathies. Neuron. 2025; 113: 2556\u20132581.","DOI":"10.1016\/j.neuron.2025.04.006"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"Sonnino S, Aureli M, Grassi S, Mauri L, Prioni S, Prinetti A. Lipid rafts in neurodegeneration and neuroprotection. Molecular Neurobiology. 2014; 50: 130\u2013148.","DOI":"10.1007\/s12035-013-8614-4"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Sharma S, Wahl D, Risen S, Gilberto VS, Chatterjee A, Moreno JA, et al. Brain-penetrant NF-\u03baB and NLRP3 targeting nanoligomers are therapeutic in ALS and Alzheimer\u2019s disease human organoid and mouse models. bioRxiv. 2024.  (preprint)","DOI":"10.1101\/2024.03.07.583991"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Ulland TK, Ewald AC, Knutson AO, Marino KM, Smith SMC, Watters JJ. Alzheimer\u2019s Disease, Sleep Disordered Breathing, and Microglia: Puzzling out a Common Link. Cells. 2021; 10: 2907.","DOI":"10.3390\/cells10112907"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"Shang P, Zhang Y, Ma D, Hao Y, Wang X, Xin M, et al. Inflammation resolution and specialized pro-resolving lipid mediators in CNS diseases. Expert Opinion on Therapeutic Targets. 2019; 23: 967\u2013986.","DOI":"10.1080\/14728222.2019.1691525"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"Sarkar C, Chen Y, Nguyen DP, Weldemariam MM, Morel Y, Mehrabani-Tabari A, et al. Lysosomal multi-omics reveals altered sphingolipid catabolism as driver of lysosomal dysfunction in the aging brain. bioRxiv. 2025.  (preprint)","DOI":"10.1101\/2025.09.10.675421"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"Agosta F, Vossel KA, Miller BL, Migliaccio R, Bonasera SJ, Filippi M, et al. Apolipoprotein E \u03b54 is associated with disease-specific effects on brain atrophy in Alzheimer\u2019s disease and frontotemporal dementia. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106: 2018\u20132022.","DOI":"10.1073\/pnas.0812697106"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"Cheng GW, Mok KK, Yeung SH, Kofler J, Herrup K, Tse KH. Apolipoprotein E \u03b54 mediates myelin breakdown by targeting oligodendrocytes in sporadic Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2022; 81: 717-30.","DOI":"10.1093\/jnen\/nlac054"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"Farmer BC, Kluemper J, Johnson LA. Apolipoprotein E4 alters astrocyte fatty acid metabolism and lipid droplet formation. Cells. 2019; 8: 182.","DOI":"10.3390\/cells8020182"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"Windham IA, Powers AE, Ragusa JV, Wallace ED, Zanellati MC, Williams VH, et al. APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size. Journal of Cell Biology. 2024; 223: e202305003.","DOI":"10.1083\/jcb.202305003"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"Lanfranco MF, Ng CA, Rebeck GW. ApoE Lipidation as a Therapeutic Target in Alzheimer\u2019s Disease. International Journal of Molecular Sciences. 2020; 21: 6336.","DOI":"10.3390\/ijms21176336"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Husain MA, Laurent B, Plourde M. APOE and Alzheimer\u2019s Disease: From Lipid Transport to Physiopathology and Therapeutics. Frontiers in Neuroscience. 2021; 15: 630502.","DOI":"10.3389\/fnins.2021.630502"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"Qian XH, Chen SY, Liu XL, Tang HD. ABCA7-Associated Clinical Features and Molecular Mechanisms in Alzheimer\u2019s Disease. Molecular Neurobiology. 2023; 60: 5548\u20135556.","DOI":"10.1007\/s12035-023-03414-8"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"Furuhashi M, Ishimura S, Ota H, Miura T. Lipid chaperones and metabolic inflammation. International Journal of Inflammation. 2011; 2011: 642612.","DOI":"10.4061\/2011\/642612"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Eggert S, Thomas C, Kins S, Hermey G. Trafficking in Alzheimer\u2019s Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin. Molecular Neurobiology. 2018; 55: 5809\u20135829.","DOI":"10.1007\/s12035-017-0806-x"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Limone A, Veneruso I, D\u2019Argenio V, Sarnataro D. Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer\u2019s disease. Journal of Cellular Physiology. 2022; 237: 3803\u20133815.","DOI":"10.1002\/jcp.30864"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"JeBailey L, Wanono O, Niu W, Roessler J, Rudich A, Klip A. Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Diabetes. 2007; 56: 394\u2013403.","DOI":"10.2337\/db06-0823"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"Xu Z, He S, Begum MM, Han X. Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications. Antioxidants & Redox Signaling. 2024; 41: 1073\u20131099.","DOI":"10.1089\/ars.2024.0676"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"Rojas-Morales P, Pedraza-Chaverri J, Tapia E. Ketone bodies, stress response, and redox homeostasis. Redox Biology. 2020; 29: 101395.","DOI":"10.1016\/j.redox.2019.101395"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"Lozoya OA, Wang T, Grenet D, Wolfgang TC, Sobhany M, Ganini da Silva D, et al. Mitochondrial acetyl-CoA reversibly regulates locus-specific histone acetylation and gene expression. Life Science Alliance. 2019; 2: e201800228.","DOI":"10.26508\/lsa.201800228"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"Ayala A, Mu\u00f1oz MF, Arg\u00fcelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity. 2014; 2014: 360438.","DOI":"10.1155\/2014\/360438"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"Arjmand S, Ilaghi M, Sisakht AK, Guldager MB, Wegener G, Landau AM, et al. Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer\u2019s disease: A focused review. Basic & Clinical Pharmacology & Toxicology. 2024; 135: 115\u2013132.","DOI":"10.1111\/bcpt.14035"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Ghosh S. 7-Ketocholesterol: occurrence, biological activities, and plausible remediation. Redox Experimental Medicine. 2025; 2025: e250009.","DOI":"10.1530\/REM-25-0009"},{"key":"ref97","doi-asserted-by":"publisher","unstructured":"Michno W, Wehrli PM, Zetterberg H, Blennow K, Hanrieder J. GM1 locates to mature amyloid structures implicating a prominent role for glycolipid-protein interactions in Alzheimer pathology. Biochimica et Biophysica Acta. Proteins and Proteomics. 2019; 1867: 458\u2013467.","DOI":"10.1016\/j.bbapap.2018.09.010"},{"key":"ref98","doi-asserted-by":"publisher","unstructured":"Huynh K, Lim WL, Giles C, Jayawardana KS, Salim A, Mellett NA, et al. Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer\u2019s disease. Nature communications. 2020; 11: 5698.","DOI":"10.1038\/s41467-020-19473-7"},{"key":"ref99","doi-asserted-by":"publisher","unstructured":"Chua XY, Torta F, Chong JR, Venketasubramanian N, Hilal S, Wenk MR, et al. Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer\u2019s disease and vascular dementia. Alzheimer\u2019s Research & Therapy. 2023; 15: 214.","DOI":"10.1186\/s13195-023-01359-7"},{"key":"ref100","doi-asserted-by":"publisher","unstructured":"Ademowo OS, Dias HKI, Milic I, Devitt A, Moran R, Mulcahy R, et al. Phospholipid oxidation and carotenoid supplementation in Alzheimer\u2019s disease patients. Free Radical Biology & Medicine. 2017; 108: 77\u201385.","DOI":"10.1016\/j.freeradbiomed.2017.03.008"},{"key":"ref101","doi-asserted-by":"publisher","unstructured":"Sodero AO. 24S-hydroxycholesterol: Cellular effects and variations in brain diseases. Journal of Neurochemistry. 2021; 157: 899\u2013918.","DOI":"10.1111\/jnc.15228"},{"key":"ref102","doi-asserted-by":"publisher","unstructured":"Casas-Fern\u00e1ndez E, Pe\u00f1a-Bautista C, Baquero M, Ch\u00e1fer-Peric\u00e1s C. Lipids as Early and Minimally Invasive Biomarkers for Alzheimer\u2019s Disease. Current Neuropharmacology. 2022; 20: 1613\u20131631.","DOI":"10.2174\/1570159X19666211102150955"},{"key":"ref103","doi-asserted-by":"publisher","unstructured":"Chiurchi\u00f9 V, Tiberi M, Matteocci A, Fazio F, Siffeti H, Saracini S, et al. Lipidomics of Bioactive Lipids in Alzheimer\u2019s and Parkinson\u2019s Diseases: Where Are We? International Journal of Molecular Sciences. 2022; 23: 6235.","DOI":"10.3390\/ijms23116235"},{"key":"ref104","doi-asserted-by":"publisher","unstructured":"Yoon JH, Seo Y, Jo YS, Lee S, Cho E, Cazenave-Gassiot A, et al. Brain lipidomics: From functional landscape to clinical significance. Science Advances. 2022; 8: eadc9317.","DOI":"10.1126\/sciadv.adc9317"},{"key":"ref105","doi-asserted-by":"publisher","unstructured":"Dagliati A, Peek N, Brinton RD, Geifman N. Sex and APOE genotype differences related to statin use in the aging population. Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions. 2021; 7: e12156.","DOI":"10.1002\/trc2.12156"},{"key":"ref106","doi-asserted-by":"publisher","unstructured":"Williams T, Borchelt DR, Chakrabarty P. Therapeutic approaches targeting Apolipoprotein E function in Alzheimer\u2019s disease. Molecular Neurodegeneration. 2020; 15: 8.","DOI":"10.1186\/s13024-020-0358-9"},{"key":"ref107","doi-asserted-by":"publisher","unstructured":"Tang BL. Alzheimer\u2019s disease: channeling APP to non-amyloidogenic processing. Biochemical and Biophysical Research Communications. 2005; 331: 375\u2013378.","DOI":"10.1016\/j.bbrc.2005.03.074"},{"key":"ref108","doi-asserted-by":"publisher","unstructured":"Kivipelto M, Palmer K, Hoang TD, Yaffe K. Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes. Stroke. 2022; 53: 444\u2013456.","DOI":"10.1161\/STROKEAHA.121.032614"},{"key":"ref109","doi-asserted-by":"publisher","unstructured":"Casali BT, Reed-Geaghan EG, Landreth GE. Nuclear receptor agonist-driven modification of inflammation and amyloid pathology enhances and sustains cognitive improvements in a mouse model of Alzheimer\u2019s disease. Journal of Neuroinflammation. 2018; 15: 43.","DOI":"10.1186\/s12974-018-1091-y"},{"key":"ref110","doi-asserted-by":"publisher","unstructured":"Strosznajder AK, W\u00f3jtowicz S, Je\u017cyna MJ, Sun GY, Strosznajder JB. Recent Insights on the Role of PPAR-\u03b2\/\u03b4 in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy. Neuromolecular Medicine. 2021; 23: 86\u201398.","DOI":"10.1007\/s12017-020-08629-9"},{"key":"ref111","doi-asserted-by":"publisher","unstructured":"Pizcueta P, Vergara C, Emanuele M, Vilalta A, Rodr\u00edguez-Pascau L, Martinell M. Development of PPAR\u03b3 Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate. International Journal of Molecular Sciences. 2023; 24: 3201.","DOI":"10.3390\/ijms24043201"},{"key":"ref112","doi-asserted-by":"publisher","unstructured":"Chen Y, Touboul R, Chen Y, Chang CL. Strategic delivery of omega-3 fatty acids for modulating inflammatory neurodegenerative diseases. Frontiers in Aging Neuroscience. 2025; 17: 1535094.","DOI":"10.3389\/fnagi.2025.1535094"},{"key":"ref113","doi-asserted-by":"publisher","unstructured":"Afshordel S, Hagl S, Werner D, R\u00f6hner N, K\u00f6gel D, Bazan NG, et al. Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging\u2013impact of Bcl-2 and NPD-1 like metabolites. Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2015; 92: 23\u201331.","DOI":"10.1016\/j.plefa.2014.05.008"},{"key":"ref114","doi-asserted-by":"publisher","unstructured":"D\u00edaz M, Mesa-Herrera F, Mar\u00edn R. DHA and Its Elaborated Modulation of Antioxidant Defenses of the Brain: Implications in Aging and AD Neurodegeneration. Antioxidants. 2021; 10: 907.","DOI":"10.3390\/antiox10060907"},{"key":"ref115","doi-asserted-by":"publisher","unstructured":"Zhang H, Ma Q, Zhang YW, Xu H. Proteolytic processing of Alzheimer\u2019s \u03b2-amyloid precursor protein. Journal of Neurochemistry. 2012; 120: 9\u201321.","DOI":"10.1111\/j.1471-4159.2011.07519.x"},{"key":"ref116","doi-asserted-by":"publisher","unstructured":"Du Z, Li M, Ren J, Qu X. Current Strategies for Modulating A\u03b2 Aggregation with Multifunctional Agents. Accounts of Chemical Research. 2021; 54: 2172\u20132184.","DOI":"10.1021\/acs.accounts.1c00055"},{"key":"ref117","doi-asserted-by":"publisher","unstructured":"Usova EI, Alieva AS, Yakovlev AN, Alieva MS, Prokhorikhin AA, Konradi AO, et al. Integrative Analysis of Multi-Omics and Genetic Approaches-A New Level in Atherosclerotic Cardiovascular Risk Prediction. Biomolecules. 2021; 11: 1597.","DOI":"10.3390\/biom11111597"},{"key":"ref118","doi-asserted-by":"publisher","unstructured":"Geltinger F, Schartel L, Wiederstein M, Tevini J, Aigner E, Felder TK, et al. Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease. Molecules. 2020; 25: 5053.","DOI":"10.3390\/molecules25215053"},{"key":"ref119","doi-asserted-by":"publisher","unstructured":"Demarquoy J, Le Borgne F. Crosstalk between mitochondria and peroxisomes. World Journal of Biological Chemistry. 2015; 6: 301\u2013309.","DOI":"10.4331\/wjbc.v6.i4.301"},{"key":"ref120","doi-asserted-by":"publisher","unstructured":"Mills JD, Nalpathamkalam T, Jacobs HIL, Janitz C, Merico D, Hu P, et al. RNA-Seq analysis of the parietal cortex in Alzheimer\u2019s disease reveals alternatively spliced isoforms related to lipid metabolism. Neuroscience Letters. 2013; 536: 90\u201395.","DOI":"10.1016\/j.neulet.2012.12.042"},{"key":"ref121","doi-asserted-by":"publisher","unstructured":"Kope\u0107 K, Koziorowski D, Szlufik S. The Therapeutic Potential of Glymphatic System Activity to Reduce the Pathogenic Accumulation of Cytotoxic Proteins in Alzheimer\u2019s Disease. International Journal of Molecular Sciences. 2025; 26: 7552.","DOI":"10.3390\/ijms26157552"},{"key":"ref122","doi-asserted-by":"publisher","unstructured":"Silva I, Silva J, Ferreira R, Trigo D. Glymphatic system, AQP4, and their implications in Alzheimer\u2019s disease. Neurological Research and Practice. 2021; 3: 5.","DOI":"10.1186\/s42466-021-00102-7"},{"key":"ref123","doi-asserted-by":"publisher","unstructured":"Decourt B, D\u2019Souza GX, Shi J, Ritter A, Suazo J, Sabbagh MN. The Cause of Alzheimer\u2019s Disease: The Theory of Multipathology Convergence to Chronic Neuronal Stress. Aging and Disease. 2022; 13: 37\u201360.","DOI":"10.14336\/AD.2021.0529"},{"key":"ref124","doi-asserted-by":"publisher","unstructured":"Kumar R, Johar R, Caruso G, Singh M, Chandra M, Igwegbe CA, et al. Pathophysiology of Alzheimer\u2019s disease: advances in drug development and therapeutic innovations. Chemical Biology Letters. 2025; 12: 1264.","DOI":"10.62110\/sciencein.cbl.2025.v12.1264"},{"key":"ref125","doi-asserted-by":"publisher","unstructured":"Hampel H, Au R, Mattke S, van der Flier WM, Aisen P, Apostolova L, et al. Designing the next-generation clinical care pathway for Alzheimer\u2019s disease. Nature Aging. 2022; 2: 692\u2013703.","DOI":"10.1038\/s43587-022-00269-x"},{"key":"ref126","doi-asserted-by":"publisher","unstructured":"Brandts J, Ray KK. Novel and future lipid-modulating therapies for the prevention of cardiovascular disease. Nature Reviews. Cardiology. 2023; 20: 600\u2013616.","DOI":"10.1038\/s41569-023-00860-8"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/4\/10.31083\/JIN48436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:27:18Z","timestamp":1777451238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/25\/4\/10.31083\/JIN48436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":126,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"alternative-id":["S0219-6352(26)01115-0"],"URL":"https:\/\/doi.org\/10.31083\/jin48436","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"article-number":"48436"}}