{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:04:28Z","timestamp":1785416668568,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032554","name":"Peking University Shenzhen Hospital","doi-asserted-by":"crossref","award":["LCYJZD2022006"],"award-info":[{"award-number":["LCYJZD2022006"]}],"id":[{"id":"10.13039\/100032554","id-type":"DOI","asserted-by":"crossref"}]},{"award":["LCYJZD2022006"],"award-info":[{"award-number":["LCYJZD2022006"]}],"id":[{"id":"https:\/\/ror.org\/03kkjyb15","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Previous metabolomics studies on Alzheimer\u2019s disease (AD) have predominantly focused on Western populations, leaving Chinese cohorts and disease stage-specific data largely unexplored. Objectives: To characterize metabolic alterations across different clinical stages of AD in a Chinese population and identify early diagnostic biomarkers. Methods: We enrolled 172 participants, including patients with AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), vascular cognitive impairment (VCI), and healthy controls (HC). Untargeted metabolomics (LC-MS and GC-MS) was performed on plasma samples, integrated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessments. Data were analyzed using multivariate statistics, pathway enrichment, and ROC modeling. Results: Distinct metabolic profiles emerged across disease stages, with phospholipids, ceramides, and glucose metabolites prominently enriched in glycerophospholipid, sphingolipid, and glucose pathways. A 16-metabolite panel achieved robust discrimination between AD+MCI and HC+VCI+SCD (AUC = 0.804). Specific metabolites, including ceramides, dihydroceramides, phosphatidylinositol, phosphatidylcholine, and glycodeoxycholic acid, correlated significantly with cognitive function and disease progression. Conclusions: This study reveals stage-specific metabolic dysregulation in Chinese AD patients and identifies potential plasma biomarkers for early detection, offering insights into AD pathogenesis. Trial registration number ChiCTR2400092653.<\/jats:p>","DOI":"10.3390\/metabo16060377","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of Plasma Metabolomic Biomarker Panels in Early Diagnosis and Disease Staging of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen 518036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen 518036, China"},{"name":"Department of Neurology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Second People\u2019s Hospital, Shenzhen 518036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital, Shenzhen 518036, China"},{"name":"Shenzhen Key Laboratory for Neuronal Structural Biology, Shenzhen Peking University\u2014The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Twarowski, B., and Herbet, M. (2023). Inflammatory Processes in Alzheimer\u2019s Disease-Pathomechanism, Diagnosis and Treatment: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076518"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.14283\/jpad.2021.15","article-title":"The Epidemiology of Alzheimer\u2019s Disease Modifiable Risk Factors and Prevention","volume":"8","author":"Zhang","year":"2021","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ma, C., Hong, F., and Yang, S. (2022). Amyloidosis in Alzheimer\u2019s Disease: Pathogeny, Etiology, and Related Therapeutic Directions. Molecules, 27.","DOI":"10.3390\/molecules27041210"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13024-020-00391-7","article-title":"Molecular and cellular mechanisms underlying the pathogenesis of Alzhe imer\u2019s disease","volume":"15","author":"Guo","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jchromb.2017.02.008","article-title":"Metabolomics in Alzheimer\u2019s disease: The need of complementary analyti cal platforms for the identification of biomarkers to unravel the unde rlying pathology","volume":"1071","author":"Sayago","year":"2017","journal-title":"J. Chromatogr. B"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Graham, S.F., Chevallier, O.P., Elliott, C.T., H\u00f6lscher, C., Johnston, J., McGuinness, B., Kehoe, P.G., Passmore, A.P., and Green, B.D. (2015). Untargeted Metabolomic Analysis of Human Plasma Indicates Differential ly Affected Polyamine and L-Arginine Metabolism in Mild Cognitive Impa irment Subjects Converting to Alzheimer\u2019s Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119452"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"160","DOI":"10.14283\/jpad.2018.25","article-title":"Turning Point towards Blood Biomarker-Guided Targeted Therapy for Prec ision Medicine in Alzheimer\u2019s Disease","volume":"5","author":"Hampel","year":"2018","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2174\/1567205013666160129095138","article-title":"Metabolomic-Driven Elucidation of Serum Disturbances Associated with A lzheimer\u2019;s Disease and Mild Cognitive Impairment","volume":"13","author":"Barbas","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.4155\/bio-2018-0135","article-title":"Next-Generation Biomarker Discovery in Alzheimer\u2019s Disease Using Metab olomics\u2014From Animal to Human Studies","volume":"10","author":"Hurtado","year":"2018","journal-title":"Bioanalysis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neurobiolaging.2019.10.014","article-title":"Brain and blood metabolome for Alzheimer\u2019s dementia: Findings from a t argeted metabolomics analysis","volume":"86","author":"Huo","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The Human Metabolome Database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.tibs.2017.01.004","article-title":"Metabolomics: A Primer","volume":"42","author":"Liu","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrm3314","article-title":"Innovation: Metabolomics: The apogee of the omics trilogy","volume":"13","author":"Patti","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13195-024-01542-4","article-title":"Association of oxidative stress and inflammatory metabolites with Alzheimer\u2019s disease cerebrospinal fluid biomarkers in mild cognitive impairment","volume":"16","author":"Ahmad","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wilkins, J.M., and Trushina, E. (2017). Application of Metabolomics in Alzheimer\u2019s Disease. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00719"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/s12276-023-00967-5","article-title":"Altered acylcarnitine metabolism and inflexible mitochondrial fuel utilization characterize the loss of neonatal myocardial regeneration capacity","volume":"55","author":"Kankuri","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_18","first-page":"635","article-title":"The Mental Status Examination","volume":"94","author":"Norris","year":"2016","journal-title":"Am. Fam. Physician"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13007-016-0146-2","article-title":"Protocol: A fast, comprehensive and reproducible one-step extraction method for the rapid preparation of polar and semi-polar metabolites, lipids, proteins, starch and cell wall polymers from a single sample","volume":"12","author":"Salem","year":"2016","journal-title":"Plant Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cuadros-Inostroza, A., Caldana, C., Redestig, H., Kusano, M., Lisec, J., Pe\u00f1a-Cort\u00e9s, H., Willmitzer, L., and Hannah, M.A. (2009). TargetSearch\u2014A Bioconductor package for the efficient preprocessing of GC-MS metabolite profiling data. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-428"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13024-025-00803-6","article-title":"Lipidome disruption in Alzheimer\u2019s disease brain: Detection, pathological mechanisms, and therapeutic implications","volume":"20","author":"He","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cao, Y., Zhao, L.W., Chen, Z.X., and Li, S.H. (2024). New insights in lipid metabolism: Potential therapeutic targets for the treatment of Alzheimer\u2019s disease. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1430465"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s10571-025-01648-9","article-title":"Research Progress of Lipid Metabolism-Mediated Neuroinflammation in Alzheimer\u2019s Disease","volume":"46","author":"Shen","year":"2025","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fu, Y., Wang, Z.T., Huang, L.Y., Tan, C.C., Cao, X.P., and Tan, L. (2022). Heart fatty acid-binding protein is associated with phosphorylated tau and longitudinal cognitive changes. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.1008780"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1194\/jlr.P700023-JLR200","article-title":"Peripheral ethanolamine plasmalogen deficiency: A logical causative factor in Alzheimer\u2019s disease and dementia","volume":"48","author":"Goodenowe","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1139\/jpn.090059","article-title":"Circulating plasmalogen levels and Alzheimer Disease Assessment Scale-Cognitive scores in Alzheimer patients","volume":"35","author":"Wood","year":"2010","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3233\/JAD-2005-8304","article-title":"Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer\u2019s disease: Link to brain reductions in acetylcholine","volume":"8","author":"Rivera","year":"2005","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3233\/JAD-2005-7107","article-title":"Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer\u2019s disease\u2014Is this type 3 diabetes?","volume":"7","author":"Steen","year":"2005","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1084\/jem.20160493","article-title":"Changes in insulin and insulin signaling in Alzheimer\u2019s disease: Cause or consequence?","volume":"213","author":"Stanley","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.3233\/JAD-230061","article-title":"Accelerated Breakdown of Phosphatidylcholine and Phosphatidylethanolamine Is a Predominant Brain Metabolic Defect in Alzheimer\u2019s Disease","volume":"93","author":"Blusztajn","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1096\/fj.201801412R","article-title":"Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer\u2019s disease","volume":"33","author":"Patrick","year":"2019","journal-title":"FASEB J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.brainresbull.2022.08.009","article-title":"Decreases of ethanolamine plasmalogen and phosphatidylcholine in erythrocyte are a common phenomenon in Alzheimer\u2019s, Parkinson\u2019s, and coronary artery diseases","volume":"189","author":"Mawatari","year":"2022","journal-title":"Brain Res. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.bbamem.2018.03.026","article-title":"Physiologically-relevant levels of sphingomyelin, but not GM1, induces a beta-sheet-rich structure in the amyloid-beta(1-42) monomer","volume":"1860","author":"Owen","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/j.1440-1681.2006.04467.x","article-title":"Docosahexaenoic acid-induced protective effect against impaired learning in amyloid beta-infused rats is associated with increased synaptosomal membrane fluidity","volume":"33","author":"Hashimoto","year":"2006","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.3945\/jn.108.096016","article-title":"Docosahexaenoic acid and the aging brain","volume":"138","author":"Lukiw","year":"2008","journal-title":"J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Codini, M., Garcia-Gil, M., and Albi, E. (2021). Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020726"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1016\/j.bbamem.2009.08.016","article-title":"Sphingolipid\/cholesterol regulation of neurotransmitter receptor conformation and function","volume":"1788","author":"Fantini","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1002\/1873-3468.12825","article-title":"Metabolism and functions of docosahexaenoic acid-containing membrane glycerophospholipids","volume":"591","author":"Hishikawa","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1038\/s12276-024-01273-4","article-title":"Cholesterol imbalance and neurotransmission defects in neurodegeneration","volume":"56","author":"Shin","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e23428","DOI":"10.1096\/fj.202301976R","article-title":"Group III secreted phospholipase A(2) -driven lysophospholipid pathway protects against allergic asthma","volume":"38","author":"Takagi","year":"2024","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.redox.2017.04.030","article-title":"Shotgun lipidomics in substantiating lipid peroxidation in redox biology: Methods and applications","volume":"12","author":"Hu","year":"2017","journal-title":"Redox Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/jnc.16042","article-title":"Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Abeta plaques in mouse and human brains","volume":"168","author":"Huang","year":"2024","journal-title":"J. Neurochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-3084(00)00128-6","article-title":"Glycerophospholipids in brain: Their metabolism, incorporation into membranes, functions, and involvement in neurological disorders","volume":"106","author":"Farooqui","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1023\/A:1027380331807","article-title":"Membrane phospholipid alterations in Alzheimer\u2019s disease: Deficiency of ethanolamine plasmalogens","volume":"22","author":"Farooqui","year":"1997","journal-title":"Neurochem. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jpba.2014.10.009","article-title":"Metabolomic screening of regional brain alterations in the APP\/PS1 transgenic model of Alzheimer\u2019s disease by direct infusion mass spectrometry","volume":"102","author":"Vitorica","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ma, L., Wang, J., Zhou, R., Chen, M., Huang, Z., and Lin, S. (2025). Traditional Chinese Medicine-derived formulations and extracts modulating the PI3K\/AKT pathway in Alzheimer\u2019s disease. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1528919"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hwang, B.Y., Seo, J.W., Muftuoglu, C., Mert, U., Guldaval, F., Asadi, M., Karakus, H.S., Goksel, T., Veral, A., and Caner, A. (2023). Salivary Lipids of Patients with Non-Small Cell Lung Cancer Show Perturbation with Respect to Plasma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814264"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100504","DOI":"10.1016\/j.jlr.2024.100504","article-title":"Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model","volume":"65","author":"Slijkhuis","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_51","first-page":"105","article-title":"A three-year follow-up study on the transfer of mild cognitive impairment to Alzheimer\u2019s disease among the elderly in Taiyuan city","volume":"32","author":"Wang","year":"2011","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1042\/CS20150351","article-title":"LDL-lipids from patients with hypercholesterolaemia and Alzheimer\u2019s disease are inflammatory to microvascular endothelial cells: Mitigation by statin intervention","volume":"129","author":"Dias","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sabogal-Gu\u00e1queta, A.M., Villamil-Ortiz, J.G., Arias-Londo\u00f1o, J.D., and Cardona-G\u00f3mez, G.P. (2018). Inverse Phosphatidylcholine\/Phosphatidylinositol Levels as Peripheral Biomarkers and Phosphatidylcholine\/Lysophosphatidylethanolamine-Phosphatidylserine as Hippocampal Indicator of Postischemic Cognitive Impairment in Rats. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00989"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gai, X., Guo, C., Zhang, L., Zhang, L., Abulikemu, M., Wang, J., Zhou, Q., Chen, Y., Sun, Y., and Chang, C. (2021). Serum Glycerophospholipid Profile in Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.646010"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Xu, J., and Huang, X. (2020). Lipid Metabolism at Membrane Contacts: Dynamics and Functions Beyond Lipid Homeostasis. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.615856"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5436","DOI":"10.1007\/s12035-018-1448-3","article-title":"The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer\u2019s Disease and Other Neurodegenerative Disorders","volume":"56","author":"Czubowicz","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.neurobiolaging.2007.07.024","article-title":"ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer\u2019s but not normal brain","volume":"30","author":"Bandaru","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1124\/mol.106.033738","article-title":"Critical role for sphingosine kinase-1 in regulating survival of neuroblastoma cells exposed to amyloid-beta peptide","volume":"72","author":"Pchejetski","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40035-026-00537-5","article-title":"Molecular mechanisms of exercise-induced improvements in Alzheimer\u2019s disease: A focus on lipid homeostasis","volume":"15","author":"Zhou","year":"2026","journal-title":"Transl. Neurodegener."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1042\/BJ20050700","article-title":"A TrkA-to-p75NTR molecular switch activates amyloid beta-peptide generation during aging","volume":"391","author":"Costantini","year":"2005","journal-title":"Biochem. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1073\/pnas.0305799101","article-title":"Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer\u2019s disease","volume":"101","author":"Cutler","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.neuroscience.2004.08.056","article-title":"Astroglial expression of ceramide in Alzheimer\u2019s disease brains: A role during neuronal apoptosis","volume":"130","author":"Satoi","year":"2005","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3233\/JAD-2011-111202","article-title":"Increased ceramide in brains with Alzheimer\u2019s and other neurodegenerative diseases","volume":"29","author":"Filippov","year":"2012","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Chowdhury, M.R., Jin, H.K., and Bae, J.S. (2022). Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer\u2019s Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081956"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.neurobiolaging.2014.02.005","article-title":"Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer\u2019s disease and facilitates APP\/BACE1 interactions","volume":"35","author":"Fabelo","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"32570","DOI":"10.3402\/jev.v5.32570","article-title":"High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources","volume":"5","author":"Haraszti","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e12089","DOI":"10.1002\/jev2.12089","article-title":"Characterization of brain-derived extracellular vesicle lipids in Alzheimer\u2019s disease","volume":"10","author":"Su","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"168464","DOI":"10.1016\/j.jmb.2024.168464","article-title":"Impact of Membrane Phospholipids and Exosomes on the Kinetics of Amyloid-beta Fibril Assembly","volume":"436","author":"Khursheed","year":"2024","journal-title":"J. Mol. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/0022-510X(91)90249-7","article-title":"Coronal reconstruction images of glucose metabolism in Alzheimer\u2019s disease","volume":"106","author":"Fukuyama","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_70","first-page":"2438901","article-title":"Seeking a New Paradigm for Alzheimer\u2019s Disease: Considering the Roles of Inflammation, Blood-Brain Barrier Dysfunction, and Prion Disease","volume":"2017","author":"McCaulley","year":"2017","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhang, T., Chen, D., and Lee, T.H. (2019). Phosphorylation Signaling in APP Processing in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010209"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2174\/1567205013666160930110551","article-title":"Targeting Tumor Necrosis Factor Alpha for Alzheimer\u2019s Disease","volume":"14","author":"Decourt","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1111\/j.1582-4934.2011.01318.x","article-title":"Possible implications of insulin resistance and glucose metabolism in Alzheimer\u2019s disease pathogenesis","volume":"15","author":"Bosco","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ejphar.2004.02.048","article-title":"Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer\u2019s disease","volume":"490","author":"Watson","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1749-6632.1997.tb48476.x","article-title":"Decreased brain glucose metabolism in microvessels from patients with Alzheimer\u2019s disease","volume":"826","author":"Marcus","year":"1997","journal-title":"Ann. N. Y. Acad. Sci."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/6\/377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:13:56Z","timestamp":1780373636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/6\/377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":75,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["metabo16060377"],"URL":"https:\/\/doi.org\/10.3390\/metabo16060377","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]}}}