{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:18:05Z","timestamp":1794071885393,"version":"4.8.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["25K00258"],"award-info":[{"award-number":["25K00258"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JST SPRING","award":["JPMJSP2119"],"award-info":[{"award-number":["JPMJSP2119"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and Huntington\u2019s disease (HD) are progressive neurodegenerative diseases (NDs) characterized by chronic neuronal loss. The lack of effective treatments highlights the urgent need for reliable lipid biomarkers to enable diagnosis and monitor disease progression. Previous lipidomic investigations of altered lipid metabolism have focused on a single disease type, limiting cross-disease comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We applied the untargeted liquid chromatography-mass spectrometry (LC\/MS) technique to profile brain lipidome alterations and to identify disease-specific lipid biomarkers across AD, HD, and PD. Brain tissue samples were collected from four cerebral lobes of healthy volunteers (HV,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f24) and patients diagnosed with AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f24), PD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f24), and HD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f24). All groups include three males and three females, with brain tissues from four cortical regions sacrificed from each individual.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 243 lipid molecular species spanning five major classes were annotated, revealing distinct disease-specific lipidomic profiles that differentiated HV from the AD, HD, and PD groups via multivariate analysis. Sphingomyelins and oxidized phosphatidylserine [PS (16:1\/24:0;O1)] were significantly increased, while lysophosphatidylcholines (LPC 18:2, LPC 17:2) were decreased in the AD group relative to HV. HD exhibited elevated PS (O-17:0\/22:6) and \u03c9-6 fatty acid esterified cholesteryl esters (CE 18:2, CE 20:4), alongside decreased essential neuronal lipids such as phosphatidylinositols (PI). The PD lipidome alterations closely resembled those of HD, indicating partially overlapping disruptions in brain lipid metabolism. Receiver operating characteristic analysis identified PS (16:1\/24:0;O1), PS (O-17:0\/22:6), and PI (18:1\/18:1) as potential discriminatory biomarkers with strong diagnostic performance. Regional heatmap analysis revealed significant lipid perturbations were observed in the parietal and occipital lobes across all NDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a comprehensive overview of disease- and region-specific alterations in the brain lipidome of AD, HD, and PD. The identified lipid species-PS (16:1\/24:0;O1), PS (O-17:0\/22:6), and PI (18:1\/18:1)-may serve as promising candidate biomarkers for NDs diagnosis and warrant further mechanistic and longitudinal validation with large data set.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1757306","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:08:35Z","timestamp":1770793715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Brain lipidomics for region-specific biomarker discovery in neurodegenerative diseases"],"prefix":"10.3389","volume":"18","author":[{"given":"Jayashankar","family":"Jayaprakash","sequence":"first","affiliation":[{"name":"Graduate School of Global Food Resources, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon Tebeje","family":"Gizaw","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University","place":["Addis Ababa, Ethiopia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divyavani","family":"Gowda","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Hinou","sequence":"additional","affiliation":[{"name":"Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Ichiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ping","family":"Hui","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddabasave Gowda","family":"B. Gowda","sequence":"additional","affiliation":[{"name":"Graduate School of Global Food Resources, Hokkaido University","place":["Sapporo, Japan"]},{"name":"Faculty of Health Sciences, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/mds.25729","article-title":"Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson\u2019s disease","volume":"29","author":"Abbott","year":"2014","journal-title":"Mov. Disord."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3233\/JAD-190923","article-title":"Partial mitigation of oxidized phospholipid-mediated mitochondrial dysfunction in neuronal cells by oxocarotenoids","volume":"74","author":"Ademowo","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/jdad2020017","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease: insights into pathophysiology and treatment","volume":"2","author":"Alkhalifa","year":"2025","journal-title":"J. Dement. Alzheimers Dis."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-\u03b2 and tau: the trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.addr.2020.01.004","article-title":"Fatty acid metabolism in the progression and resolution of CNS disorders","volume":"159","author":"Bogie","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nrn3887","article-title":"Spreading of pathology in neurodegenerative diseases: a focus on human studies","volume":"16","author":"Brettschneider","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1039\/d0mo00186d","article-title":"Cerebrospinal fluid lipidomics for biomarkers of Alzheimer\u2019s disease","volume":"17","author":"Byeon","year":"2021","journal-title":"Mol. Omics"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"382","DOI":"10.3389\/fnins.2019.00382","article-title":"Differential aggregation and phosphorylation of alpha synuclein in membrane compartments associated with Parkinson disease","volume":"13","author":"Canerina-Amaro","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.3390\/ijms21031161","article-title":"High-cholesterol diet decreases the level of phosphatidylinositol 4,5-bisphosphate by enhancing the expression of phospholipase C (PLC\u03b21) in rat brain","volume":"21","author":"Chun","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.addr.2019.12.003","article-title":"Sphingolipids in Alzheimer\u2019s disease, how can we target them?","volume":"159","author":"Crivelli","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/nrn3012","article-title":"Linking lipids to Alzheimer\u2019s disease: cholesterol and beyond","volume":"12","author":"Di Paolo","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.2119\/molmed.2011.00119","article-title":"Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson\u2019s disease and incidental Parkinson\u2019s disease","volume":"17","author":"Fabelo","year":"2011","journal-title":"Mol. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.molcel.2018.11.028","article-title":"Lipidomic analysis of \u03b1-synuclein neurotoxicity identifies stearoyl CoA desaturase as a target for Parkinson treatment","volume":"73","author":"Fanning","year":"2019","journal-title":"Mol. Cell"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"105933","DOI":"10.1016\/j.nbd.2022.105933","article-title":"Longitudinal spatial mapping of lipid metabolites reveals pre-symptomatic changes in the hippocampi of Huntington\u2019s disease transgenic mice","volume":"176","author":"Farzana","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1038\/s42255-025-01365-z","article-title":"The neurolipid atlas: a lipidomics resource for neurodegenerative diseases","volume":"7","author":"Feringa","year":"2025","journal-title":"Nat. Metab."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"690372","DOI":"10.3389\/fnagi.2021.690372","article-title":"Cholesterol and Alzheimer\u2019s disease; from risk genes to pathological effects","volume":"13","author":"Feringa","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3390\/biomedicines9050491","article-title":"Alteration in the cerebrospinal fluid lipidome in Parkinson\u2019s disease: a post-mortem pilot study","volume":"9","author":"Fern\u00e1ndez-Irigoyen","year":"2021","journal-title":"Biomedicine"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/s0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/S1474-4422(18)30295-3","article-title":"Global, regional, and national burden of Parkinson\u2019s disease, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"17","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019","volume":"7","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref21","article-title":"Comprehensive glycomics for the discovery of new biomarkers in neurodegenerative diseases","volume-title":"Doctoral Dissertation","author":"Gizaw","year":"2015"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"7713","DOI":"10.1016\/j.chroma.2011.07.073","article-title":"From brain to food: analysis of phosphatidylcholins, lyso-phosphatidylcholins and phosphatidylcholin-plasmalogens derivates in Alzheimer\u2019s disease human post mortem brains and mice model via mass spectrometry","volume":"1218","author":"Grimm","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","article-title":"Biomarkers for neurodegenerative diseases","volume":"27","author":"Hansson","year":"2021","journal-title":"Nat. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41531-024-00655-9","article-title":"Synaptic loss and its association with symptom severity in Parkinson\u2019s disease","volume":"10","author":"Holmes","year":"2024","journal-title":"npj Parkinsons Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"135455","DOI":"10.1016\/j.neulet.2020.135455","article-title":"Mini review: lipids in peripheral nerve disorders","volume":"740","author":"Hornemann","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e74016","DOI":"10.1371\/journal.pone.0074016","article-title":"Elevation in sphingomyelin synthase activity is associated with increases in amyloid-beta peptide generation","volume":"8","author":"Hsiao","year":"2013","journal-title":"PLoS One"},{"key":"ref27","doi-asserted-by":"publisher","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":"ref28","doi-asserted-by":"publisher","first-page":"3106145","DOI":"10.1155\/jl\/3106145","article-title":"Plasma lipidomics of preadolescent children: a Hokkaido study","volume":"2025","author":"Jayaprakash","year":"2025","journal-title":"J. Lipids"},{"key":"ref29","doi-asserted-by":"crossref","DOI":"10.1101\/2023.08.24.23294581","article-title":"Lysophosphatidylcholines are associated with P-tau181 levels in early stages of Alzheimer\u2019s disease","author":"Kalia","year":"2023"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"289","DOI":"10.18999\/nagjms.80.3.289","article-title":"Preclinical progression of neurodegenerative diseases","volume":"80","author":"Katsuno","year":"2018","journal-title":"Nagoya J. Med. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"100005","DOI":"10.1016\/j.bionps.2019.100005","article-title":"Diagnostic biomarkers of Alzheimer\u2019s disease: a state-of-the-art review","volume":"1","author":"Khoury","year":"2019","journal-title":"Biomark. Neuropsychiatry"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.neuroscience.2011.04.018","article-title":"Increased expression of acyl-coenzyme a: cholesterol acyltransferase-1 and elevated cholesteryl esters in the hippocampus after excitotoxic injury","volume":"185","author":"Kim","year":"2011","journal-title":"Neuroscience"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.neulet.2012.04.019","article-title":"Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer\u2019s disease","volume":"516","author":"Kosicek","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.3390\/ijms23031851","article-title":"A review of the common neurodegenerative disorders: current therapeutic approaches and the potential role of nanotherapeutics","volume":"23","author":"Lamptey","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: past, present and future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s12264-019-00433-1","article-title":"Biomarkers for Parkinson\u2019s disease: how good are they?","volume":"36","author":"Li","year":"2020","journal-title":"Neurosci. Bull."},{"key":"ref37","doi-asserted-by":"publisher","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":"ref38","doi-asserted-by":"publisher","first-page":"975176","DOI":"10.3389\/fnagi.2022.975176","article-title":"Phosphatidylserine, inflammation, and central nervous system diseases","volume":"14","author":"Ma","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/s41419-024-07152-0","article-title":"The link between amyloid \u03b2 and ferroptosis pathway in Alzheimer\u2019s disease progression","volume":"15","author":"Majern\u00edkov\u00e1","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"jeb245355","DOI":"10.1242\/jeb.245355","article-title":"The roles of brain lipids and polar metabolites in the hypoxia tolerance of deep-diving pinnipeds","volume":"226","author":"Martens","year":"2023","journal-title":"J. Exp. Biol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"20490","DOI":"10.1038\/s41598-020-77526-9","article-title":"Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington\u2019s disease for participants of varying functional disability: a pilot study","volume":"10","author":"McGarry","year":"2020","journal-title":"Sci. Rep."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e00525","DOI":"10.1016\/j.neurot.2025.e00525","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease: guiding the path to targeted therapies","volume":"22","author":"McGill Percy","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref43","first-page":"298","article-title":"Sex- and Regio-Specific Lipid Profiling of Shishamo and Capelin Fish by Nontargeted Liquid Chromatography\/Mass Spectrometry","volume-title":"Foods","author":"Minami","year":"2025"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"617588","DOI":"10.3389\/fnagi.2021.617588","article-title":"Mitochondrial dysfunction and oxidative stress in Alzheimer\u2019s disease","volume":"13","author":"Misrani","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"20690","DOI":"10.1021\/acs.jafc.4c05919","article-title":"Nontargeted lipidomics of Sorghum grain reveals novel fatty acid esters of hydroxy fatty acids and cultivar differences in lipid profiles","volume":"72","author":"Nath","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1111\/j.1749-6632.1991.tb00200.x","article-title":"Alterations of phospholipid metabolites in postmortem brain from patients with Alzheimer\u2019s disease","volume":"640","author":"Nitsch","year":"1991","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref47","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0022-2275(20)39619-X","article-title":"Lipid composition of the normal human brain: gray matter, white matter, and myelin","volume":"6","author":"O\u2019Brien","year":"1965","journal-title":"J. Lipid Res."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"100061","DOI":"10.1016\/j.rbc.2025.100061","article-title":"Oxidized phospholipids in ferroptosis, immunity and inflammation","volume":"14","author":"O\u2019Donnell","year":"2025","journal-title":"Redox Biochem. Chem."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"6742","DOI":"10.1038\/s41467-024-50626-0","article-title":"Multi-omic analysis of Huntington\u2019s disease reveals a compensatory astrocyte state","volume":"15","author":"Paryani","year":"2024","journal-title":"Nat. Commun."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"20314","DOI":"10.1038\/s41598-020-76973-8","article-title":"Cholesteryl ester levels are elevated in the caudate and putamen of Huntington\u2019s disease patients","volume":"10","author":"Phillips","year":"2020","journal-title":"Sci. Rep."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3892\/mi.2025.267","article-title":"Epidemiology of autonomic dysfunction in Parkinson\u2019s disease (review)","volume":"5","author":"Rissardo","year":"2025","journal-title":"Med. Int."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"805","DOI":"10.3389\/fnins.2018.00805","article-title":"Altered intracortical T1-weighted\/T2-weighted ratio signal in Huntington\u2019s disease","volume":"12","author":"Rowley","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"3694","DOI":"10.1021\/acschemneuro.5c00230","article-title":"Dysregulated lipids in Alzheimer\u2019s disease: insights into biological pathways through LC-MS\/MS analysis of human brain tissues","volume":"16","author":"Sanni","year":"2025","journal-title":"ACS Chem. Neurosci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1002\/1873-3468.14992","article-title":"The non-enzymatic oxidation of phosphatidylethanolamine and phosphatidylserine and their intriguing roles in inflammation dynamics and diseases","volume":"598","author":"Santos","year":"2024","journal-title":"FEBS Lett."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.cmet.2008.07.005","article-title":"Glutathione peroxidase 4 senses and translates oxidative stress into 12\/15-lipoxygenase dependent- and AIF-mediated cell death","volume":"8","author":"Seiler","year":"2008","journal-title":"Cell Metab."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"119","DOI":"10.37349\/ent.2024.00075","article-title":"Biomarkers in neurodegenerative diseases: a broad overview","volume":"4","author":"Selvam","year":"2024","journal-title":"Explor. Neuroprot. Ther."},{"key":"ref57","doi-asserted-by":"publisher","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":"Alzheimers Res. Ther."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1038\/s41467-022-30374-9","article-title":"PI(18:1\/18:1) is a SCD1-derived lipokine that limits stress signaling","volume":"13","author":"Th\u00fcrmer","year":"2022","journal-title":"Nat. Commun."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"850","DOI":"10.3390\/molecules30040850","article-title":"Untargeted lipidomic reveals potential biomarkers in plasma samples for the discrimination of patients affected by Parkinson\u2019s disease","volume":"30","author":"Tkachenko","year":"2025","journal-title":"Molecules"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.bbalip.2015.02.002","article-title":"PIPs in neurological diseases","volume":"1851","author":"Waugh","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"633022","DOI":"10.3389\/fnins.2021.633022","article-title":"Lipoprotein-associated phospholipase A2 is a risk factor for patients with Parkinson\u2019s disease","volume":"15","author":"Wu","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s13578-022-00828-0","article-title":"Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases","volume":"12","author":"Yang","year":"2022","journal-title":"Cell Biosci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/metabo15010010","article-title":"Lipidomics of Huntington\u2019s disease: a comprehensive review of current status and future directions","volume":"15","author":"Yilmaz","year":"","journal-title":"Metabolites"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41531-025-01023-x","article-title":"Lipid profiling of Parkinson\u2019s disease brain highlights disruption in lysophosphatidylcholines, and triacylglycerol metabolism","volume":"11","author":"Yilmaz","year":"","journal-title":"npj Parkinsons Dis."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"eadc9317","DOI":"10.1126\/sciadv.adc9317","article-title":"Brain lipidomics: from functional landscape to clinical significance","volume":"8","author":"Yoon","year":"2022","journal-title":"Sci. Adv."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/s0736-5748(00)00013-7","article-title":"Essential fatty acids and the brain: possible health implications","volume":"18","author":"Youdim","year":"2000","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"14509","DOI":"10.1038\/s41598-020-71510-z","article-title":"Untargeted lipidomics reveals progression of early Alzheimer\u2019s disease in APP\/PS1 transgenic mice","volume":"10","author":"Zhang","year":"2020","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1757306\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:08:39Z","timestamp":1770793719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1757306\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":67,"alternative-id":["10.3389\/fnagi.2026.1757306"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1757306","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"article-number":"1757306"}}