{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:06:36Z","timestamp":1789815996811,"version":"4.0.1"},"reference-count":110,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":102,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008975","name":"Universitat de Les Illes Balears","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008975","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) poses a significant global health burden, underscoring the need for early and accessible biomarkers to enable timely diagnosis and intervention. Lipids, which constitute over half of the brain\u2019s mass, play essential roles in numerous cellular processes, and their dysregulation has been increasingly implicated in AD pathophysiology. In this study, we performed lipidomic profiling of hippocampal samples derived from individuals at different Braak stages and plasma samples from patients with mild cognitive impairment (MCI), AD, and healthy controls. Parallel analyses were conducted in 5xFAD transgenic mice and wild-type littermates. Our results revealed lipid alterations across central and peripheral compartments in both human subjects and the 5xFAD mouse model. Notably, specific lipid changes identified in particular lipid species at early\/mild Braak stages or in MCI persisted into advanced stages of the disease, highlighting the systemic nature of lipid dysregulation in AD and supporting the potential of these lipid signatures as diagnostic and prognostic biomarkers.<\/jats:p>","DOI":"10.1007\/s12035-026-05849-1","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:51:39Z","timestamp":1776109899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lipidomic Analysis of Human Plasma and Hippocampus Across Alzheimer\u2019s Progression and Preclinical 5xFAD Mouse Model"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6953-5420","authenticated-orcid":false,"given":"Enrico","family":"Castroflorio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6545-1214","authenticated-orcid":false,"given":"Joan","family":"Cabot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-484X","authenticated-orcid":false,"given":"Marc","family":"Miralles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margalida","family":"Suau-Fullana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Peter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Balogh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Torok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloy","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascual","family":"Sanchez-Juan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-7028","authenticated-orcid":false,"given":"Paula","family":"F\u00e9rnandez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Llado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-182X","authenticated-orcid":false,"given":"Pablo V.","family":"Escrib\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5076-8486","authenticated-orcid":false,"given":"Manuel","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"5849_CR1","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/NRN3880","volume":"16","author":"FL Heppner","year":"2015","unstructured":"Heppner FL, Ransohoff RM, Becher B (2015) Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 16:358\u2013372. https:\/\/doi.org\/10.1038\/NRN3880","journal-title":"Nat Rev Neurosci"},{"key":"5849_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239\u2013259. https:\/\/doi.org\/10.1007\/BF00308809","journal-title":"Acta Neuropathol"},{"key":"5849_CR3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/NRNEUROL.2011.2","volume":"7","author":"C Reitz","year":"2011","unstructured":"Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7:137\u2013152. https:\/\/doi.org\/10.1038\/NRNEUROL.2011.2","journal-title":"Nat Rev Neurol"},{"key":"5849_CR4","doi-asserted-by":"publisher","unstructured":"Smith A, Rottkamp A, Nunomura A et al (2000) Oxidative stress in Alzheimer\u2019s disease. Biochim Biophys Acta Mol Basis Dis 1502:139\u2013144. https:\/\/doi.org\/10.1016\/S0925-4439(00)00040-5","DOI":"10.1016\/S0925-4439(00)00040-5"},{"key":"5849_CR5","doi-asserted-by":"publisher","unstructured":"Xu J, Begley P, Church J et al (2016) Graded perturbations of metabolism in multiple regions of human brain in Alzheimer\u2019s disease: snapshot of a pervasive metabolic disorder. Biochim Biophys Acta Mol Basis Dis 1862:1084\u20131092. https:\/\/doi.org\/10.1016\/j.bbadis.2016.03.001","DOI":"10.1016\/j.bbadis.2016.03.001"},{"key":"5849_CR6","doi-asserted-by":"publisher","unstructured":"Crary F, Trojanowski Q, Schneider A et al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755. https:\/\/doi.org\/10.1007\/S00401-014-1349-0","DOI":"10.1007\/S00401-014-1349-0"},{"key":"5849_CR7","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0B013E318232A379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960\u2013969. https:\/\/doi.org\/10.1097\/NEN.0B013E318232A379","journal-title":"J Neuropathol Exp Neurol"},{"key":"5849_CR8","doi-asserted-by":"publisher","first-page":"31","DOI":"10.17879\/FREENEUROPATHOLOGY-2020-3025","volume":"1","author":"LC Walker","year":"2020","unstructured":"Walker LC (2020) A\u03b2 plaques. Free Neuropathol 1:31. https:\/\/doi.org\/10.17879\/FREENEUROPATHOLOGY-2020-3025","journal-title":"Free Neuropathol"},{"key":"5849_CR9","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/S1474-4422(11)70307-6","volume":"11","author":"EE Smith","year":"2012","unstructured":"Smith EE, Schneider JA, Wardlaw JM, Greenberg SM (2012) Cerebral microinfarcts: the invisible lesions. Lancet Neurol 11:272. https:\/\/doi.org\/10.1016\/S1474-4422(11)70307-6","journal-title":"Lancet Neurol"},{"key":"5849_CR10","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1056\/NEJMOA2212948","volume":"388","author":"CH van D","year":"2023","unstructured":"van D CH, S CJ, A P et al (2023) Lecanemab in early Alzheimer\u2019s disease. N Engl J Med 388:142\u2013143. https:\/\/doi.org\/10.1056\/NEJMOA2212948","journal-title":"N Engl J Med"},{"issue":"4","key":"5849_CR11","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/s41582-024-00942-2","volume":"20","author":"J Therriault","year":"2024","unstructured":"Therriault J, Schindler SE, Salvad\u00f3 G et al (2024) Biomarker-based staging of Alzheimer disease: rationale and clinical applications. Nat Rev Neurol 20(4):232\u2013244. https:\/\/doi.org\/10.1038\/s41582-024-00942-2","journal-title":"Nat Rev Neurol"},{"key":"5849_CR12","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/NRM2330","volume":"9","author":"G Van Meer","year":"2008","unstructured":"Van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112\u2013124. https:\/\/doi.org\/10.1038\/NRM2330","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"5849_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-021-01362-2","volume":"11","author":"Y Liu","year":"2021","unstructured":"Liu Y, Thalamuthu A, Mather KA et al (2021) Plasma lipidome is dysregulated in Alzheimer\u2019s disease and is associated with disease risk genes. Transl Psychiatry 11(1):1\u201318. https:\/\/doi.org\/10.1038\/s41398-021-01362-2","journal-title":"Transl Psychiatry"},{"issue":"4","key":"5849_CR14","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/s41593-023-01298-4","volume":"26","author":"C Yan","year":"2023","unstructured":"Yan C, Chen ZP (2023) Abnormal lipid metabolism shapes astrocyte reactivity in patients with epilepsy. Nat Neurosci 26(4):535\u2013536. https:\/\/doi.org\/10.1038\/s41593-023-01298-4","journal-title":"Nat Neurosci"},{"key":"5849_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/S42003-024-07034-3","author":"H Meng","year":"2024","unstructured":"Meng H, Elliott A, Mansfield J et al (2024) Identification of tauopathy-associated lipid signatures in Alzheimer\u2019s disease mouse brain using label-free chemical imaging. Commun Biol. https:\/\/doi.org\/10.1038\/S42003-024-07034-3","journal-title":"Commun Biol"},{"key":"5849_CR16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/J.MOLMED.2005.11.004","volume":"12","author":"PV Escrib\u00e1","year":"2006","unstructured":"Escrib\u00e1 PV (2006) Membrane-lipid therapy: a new approach in molecular medicine. Trends Mol Med 12:34\u201343. https:\/\/doi.org\/10.1016\/J.MOLMED.2005.11.004","journal-title":"Trends Mol Med"},{"key":"5849_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS21072322","volume":"21","author":"M Torres","year":"2020","unstructured":"Torres M, Rossell\u00f3 CA, Fern\u00e1ndez-Garc\u00eda P et al (2020) The implications for cells of the lipid switches driven by protein\u2013membrane interactions and the development of membrane lipid therapy. Int J Mol Sci 21:2322. https:\/\/doi.org\/10.3390\/IJMS21072322","journal-title":"Int J Mol Sci"},{"key":"5849_CR18","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/J.NEUROBIOLAGING.2004.02.016","volume":"25","author":"A Walter","year":"2004","unstructured":"Walter A, Korth U, Hilgert M et al (2004) Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients. Neurobiol Aging 25:1299\u20131303. https:\/\/doi.org\/10.1016\/J.NEUROBIOLAGING.2004.02.016","journal-title":"Neurobiol Aging"},{"issue":"4","key":"5849_CR19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/NM.3466","volume":"20","author":"M Mapstone","year":"2014","unstructured":"Mapstone M, Cheema AK, Fiandaca MS et al (2014) Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med 20(4):415\u2013418. https:\/\/doi.org\/10.1038\/NM.3466","journal-title":"Nat Med"},{"key":"5849_CR20","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/J.JALZ.2015.12.008","volume":"12","author":"R Casanova","year":"2016","unstructured":"Casanova R, Varma S, Simpson B et al (2016) Blood metabolite markers of preclinical Alzheimer\u2019s disease in two longitudinally followed cohorts of older individuals. Alzheimers Dement 12:815\u2013822. https:\/\/doi.org\/10.1016\/J.JALZ.2015.12.008","journal-title":"Alzheimers Dement"},{"key":"5849_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-021-22491-8","volume":"12","author":"I de Rojas","year":"2021","unstructured":"de Rojas I, Moreno-Grau S, Tesi N et al (2021) Common variants in Alzheimer\u2019s disease and risk stratification by polygenic risk scores. Nat Commun 12:3417. https:\/\/doi.org\/10.1038\/S41467-021-22491-8","journal-title":"Nat Commun"},{"key":"5849_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/S41588-022-01024-Z","volume":"54","author":"C Bellenguez","year":"2022","unstructured":"Bellenguez C, K\u00fc\u00e7\u00fckali F, Jansen IE et al (2022) New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias. Nat Genet 54:412. https:\/\/doi.org\/10.1038\/S41588-022-01024-Z","journal-title":"Nat Genet"},{"key":"5849_CR23","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.1074\/JBC.M111.274142","volume":"287","author":"RB Chan","year":"2011","unstructured":"Chan RB, Oliveira TG, Cortes EP et al (2011) Comparative lipidomic analysis of mouse and human brain with Alzheimer disease. J Biol Chem 287:2678. https:\/\/doi.org\/10.1074\/JBC.M111.274142","journal-title":"J Biol Chem"},{"key":"5849_CR24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/J.NEUROBIOLAGING.2013.08.001","volume":"35","author":"L Whiley","year":"2013","unstructured":"Whiley L, Sen A, Heaton J et al (2013) Evidence of altered phosphatidylcholine metabolism in Alzheimer\u2019s disease. Neurobiol Aging 35:271. https:\/\/doi.org\/10.1016\/J.NEUROBIOLAGING.2013.08.001","journal-title":"Neurobiol Aging"},{"key":"5849_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.JALZ.2011.10.007","volume":"8","author":"BT Hyman","year":"2012","unstructured":"Hyman BT, Phelps CH, Beach TG et al (2012) National institute on aging-Alzheimer\u2019s association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease. Alzheimers Dement 8:1\u201313. https:\/\/doi.org\/10.1016\/J.JALZ.2011.10.007","journal-title":"Alzheimers Dement"},{"key":"5849_CR26","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/S43587-022-00204-0","volume":"2","author":"J Therriault","year":"2022","unstructured":"Therriault J, Pascoal TA, Lussier FZ et al (2022) Biomarker modeling of Alzheimer\u2019s disease using PET-based Braak staging. Nat Aging 2:526\u2013535. https:\/\/doi.org\/10.1038\/S43587-022-00204-0","journal-title":"Nat Aging"},{"key":"5849_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0029851","volume":"7","author":"R Herzog","year":"2012","unstructured":"Herzog R, Schuhmann K, Schwudke D et al (2012) LipidXplorer: a software for consensual cross-platform lipidomics. PLoS ONE 7:e29851. https:\/\/doi.org\/10.1371\/JOURNAL.PONE.0029851","journal-title":"PLoS ONE"},{"key":"5849_CR28","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1194\/jlr.M033506","volume":"54","author":"G Liebisch","year":"2013","unstructured":"Liebisch G, Vizca\u00edno JA, K\u00f6feler H et al (2013) Shorthand notation for lipid structures derived from mass spectrometry. J Lipid Res 54:1523\u20131530. https:\/\/doi.org\/10.1194\/jlr.M033506","journal-title":"J Lipid Res"},{"key":"5849_CR29","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/J.NEUROSCIENCE.2024.05.031","volume":"551","author":"YW Shi","year":"2024","unstructured":"Shi YW, Xu CC, Sun CY et al (2024) GM1 ameliorates neuronal injury in rats after cerebral ischemia and reperfusion: potential contribution of effects on SPTBN1-mediated signaling. Neuroscience 551:103\u2013118. https:\/\/doi.org\/10.1016\/J.NEUROSCIENCE.2024.05.031","journal-title":"Neuroscience"},{"key":"5849_CR30","doi-asserted-by":"publisher","unstructured":"Schneider JS, Aras R, Williams CK et al (2019) GM1 ganglioside modifies \u03b1-synuclein toxicity and is neuroprotective in a rat \u03b1-synuclein model of Parkinson\u2019s disease. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-019-42847-x","DOI":"10.1038\/s41598-019-42847-x"},{"key":"5849_CR31","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/BS.PMBTS.2018.01.009","volume":"156","author":"K Furukawa","year":"2018","unstructured":"Furukawa K, Ohmi Y, Tajima O et al (2018) Gangliosides in inflammation and neurodegeneration. Prog Mol Biol Transl Sci 156:265\u2013287. https:\/\/doi.org\/10.1016\/BS.PMBTS.2018.01.009","journal-title":"Prog Mol Biol Transl Sci"},{"key":"5849_CR32","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/SJ.CDD.4401027","volume":"9","author":"BM Simon","year":"2002","unstructured":"Simon BM, Malisan F, Testi R et al (2002) Disialoganglioside GD3 is released by microglia and induces oligodendrocyte apoptosis. Cell Death Differ 9:758\u2013767. https:\/\/doi.org\/10.1038\/SJ.CDD.4401027","journal-title":"Cell Death Differ"},{"key":"5849_CR33","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/J.ACA.2019.07.060","volume":"1084","author":"X Wang","year":"2019","unstructured":"Wang X, Schmitt MV, Xu L et al (2019) Quantitative molecular tissue atlas of Bis(monoacylglycero)phosphate and phosphatidylglycerol membrane lipids in rodent organs generated by methylation assisted high resolution mass spectrometry. Anal Chim Acta 1084:60\u201370. https:\/\/doi.org\/10.1016\/J.ACA.2019.07.060","journal-title":"Anal Chim Acta"},{"key":"5849_CR34","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/S41380-022-01631-6","volume":"28","author":"A Mary","year":"2023","unstructured":"Mary A, Eysert F, Checler F, Chami M (2023) Mitophagy in Alzheimer\u2019s disease: molecular defects and therapeutic approaches. Mol Psychiatry 28:202\u2013216. https:\/\/doi.org\/10.1038\/S41380-022-01631-6","journal-title":"Mol Psychiatry"},{"key":"5849_CR35","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/ALZ.12683","volume":"19","author":"T Ashleigh","year":"2023","unstructured":"Ashleigh T, Swerdlow RH, Beal MF (2023) The role of mitochondrial dysfunction in Alzheimer\u2019s disease pathogenesis. Alzheimers Dement 19:333\u2013342. https:\/\/doi.org\/10.1002\/ALZ.12683","journal-title":"Alzheimers Dement"},{"key":"5849_CR36","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.3233\/JAD-240058","volume":"98","author":"B Polis","year":"2024","unstructured":"Polis B, Samson AO (2024) Addressing the discrepancies between animal models and human Alzheimer\u2019s disease pathology: implications for translational research. J Alzheimers Dis 98:1199\u20131218. https:\/\/doi.org\/10.3233\/JAD-240058","journal-title":"J Alzheimers Dis"},{"key":"5849_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/BS.PMBTS.2020.07.007","volume":"177","author":"LM Tai","year":"2020","unstructured":"Tai LM, Maldonado Weng J, LaDu MJ, Brady ST (2020) Relevance of transgenic mouse models for Alzheimer\u2019s disease. Prog Mol Biol Transl Sci 177:1. https:\/\/doi.org\/10.1016\/BS.PMBTS.2020.07.007","journal-title":"Prog Mol Biol Transl Sci"},{"key":"5849_CR38","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/S00401-016-1662-X","volume":"133","author":"E Drummond","year":"2016","unstructured":"Drummond E, Wisniewski T (2016) Alzheimer\u2019s disease: experimental models and reality. Acta Neuropathol 133:155. https:\/\/doi.org\/10.1007\/S00401-016-1662-X","journal-title":"Acta Neuropathol"},{"key":"5849_CR39","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1111\/FEBS.16344","volume":"290","author":"F Yin","year":"2023","unstructured":"Yin F (2023) Lipid metabolism and Alzheimer\u2019s disease: clinical evidence, mechanistic link and therapeutic promise. FEBS J 290:1420\u20131453. https:\/\/doi.org\/10.1111\/FEBS.16344","journal-title":"FEBS J"},{"issue":"5","key":"5849_CR40","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/nrn3012","volume":"12","author":"G Di Paolo","year":"2011","unstructured":"Di Paolo G, Kim TW (2011) Linking lipids to Alzheimer\u2019s disease: cholesterol and beyond. Nat Rev Neurosci 12(5):284\u2013296. https:\/\/doi.org\/10.1038\/nrn3012","journal-title":"Nat Rev Neurosci"},{"key":"5849_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/FPHYS.2020.00598","author":"H Chew","year":"2020","unstructured":"Chew H, Solomon VA, Fonteh AN (2020) Involvement of lipids in Alzheimer\u2019s disease pathology and potential therapies. Front Physiol. https:\/\/doi.org\/10.3389\/FPHYS.2020.00598","journal-title":"Front Physiol"},{"key":"5849_CR42","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/0006-8993(86)91552-0","volume":"385","author":"GS Zubenko","year":"1986","unstructured":"Zubenko GS (1986) Hippocampal membrane alteration in Alzheimer\u2019s disease. Brain Res 385:115\u2013121. https:\/\/doi.org\/10.1016\/0006-8993(86)91552-0","journal-title":"Brain Res"},{"key":"5849_CR43","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/S1474-4422(17)30091-1","volume":"16","author":"J Hardy","year":"2017","unstructured":"Hardy J (2017) Membrane damage is at the core of Alzheimer\u2019s disease. Lancet Neurol 16:342. https:\/\/doi.org\/10.1016\/S1474-4422(17)30091-1","journal-title":"Lancet Neurol"},{"key":"5849_CR44","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1038\/S41380-021-01249-0","volume":"26","author":"H Hampel","year":"2021","unstructured":"Hampel H, Hardy J, Blennow K et al (2021) The amyloid-\u03b2 pathway in Alzheimer\u2019s disease. Mol Psychiatry 26:5481\u20135503. https:\/\/doi.org\/10.1038\/S41380-021-01249-0","journal-title":"Mol Psychiatry"},{"key":"5849_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-024-50299-9","author":"S Xu","year":"2024","unstructured":"Xu S, Zhu Z, Delafield DG et al (2024) Spatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer\u2019s disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics. Nat Commun. https:\/\/doi.org\/10.1038\/S41467-024-50299-9","journal-title":"Nat Commun"},{"key":"5849_CR46","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1002\/ALZ.12714","volume":"19","author":"R Batra","year":"2022","unstructured":"Batra R, Arnold M, W\u00f6rheide MA et al (2022) The landscape of metabolic brain alterations in Alzheimer\u2019s disease. Alzheimers Dement 19:980. https:\/\/doi.org\/10.1002\/ALZ.12714","journal-title":"Alzheimers Dement"},{"key":"5849_CR47","unstructured":"Update on Dementia - Google Books. https:\/\/books.google.es\/books?hl=en&lr=&id=5cGQDwAAQBAJ&oi=fnd&pg=PA127&dq=info:u9qTRTtbhCMJ:scholar.google.com&ots=2J8iNCAbp4&sig=NC2xe72rZR9t9Jieuphd03dbi3s&redir_esc=y#v=onepage&q&f=false. Accessed 23 Apr 2025"},{"key":"5849_CR48","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/J.NEUROSCIENCE.2015.02.034","volume":"292","author":"AM Sheikh","year":"2015","unstructured":"Sheikh AM, Michikawa M, Kim SU, Nagai A (2015) Lysophosphatidylcholine increases the neurotoxicity of Alzheimer\u2019s amyloid \u03b21-42 peptide: role of oligomer formation. Neuroscience 292:159\u2013169. https:\/\/doi.org\/10.1016\/J.NEUROSCIENCE.2015.02.034","journal-title":"Neuroscience"},{"key":"5849_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-022-33881-X","author":"H Park","year":"2022","unstructured":"Park H, Hundley FV, Yu Q et al (2022) Spatial snapshots of amyloid precursor protein intramembrane processing via early endosome proteomics. Nat Commun. https:\/\/doi.org\/10.1038\/S41467-022-33881-X","journal-title":"Nat Commun"},{"key":"5849_CR50","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/EMMM.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med 8:595\u2013608. https:\/\/doi.org\/10.15252\/EMMM.201606210","journal-title":"EMBO Mol Med"},{"key":"5849_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-021-02361-5","author":"D Magaquian","year":"2021","unstructured":"Magaquian D, Delgado Oca\u00f1a S, Perez C, Banchio C (2021) Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress. Sci Rep. https:\/\/doi.org\/10.1038\/S41598-021-02361-5","journal-title":"Sci Rep"},{"key":"5849_CR52","doi-asserted-by":"publisher","first-page":"14884","DOI":"10.1021\/ACS.JAFC.0C06383","volume":"68","author":"W Tan","year":"2020","unstructured":"Tan W, Zhang Q, Dong Z et al (2020) Phosphatidylcholine ameliorates LPS-induced systemic inflammation and cognitive impairments via mediating the gut-brain axis balance. J Agric Food Chem 68:14884\u201314895. https:\/\/doi.org\/10.1021\/ACS.JAFC.0C06383","journal-title":"J Agric Food Chem"},{"issue":"Pt 1","key":"5849_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ2940001","volume":"294","author":"A Zachowski","year":"1993","unstructured":"Zachowski A (1993) Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294(Pt 1):1\u201314. https:\/\/doi.org\/10.1042\/BJ2940001","journal-title":"Biochem J"},{"key":"5849_CR54","doi-asserted-by":"publisher","DOI":"10.1096\/FASEBJ.29.1_SUPPLEMENT.568.34","volume":"29","author":"S Hou","year":"2015","unstructured":"Hou S, Zhao M (2015) Distribution of phosphatidylethanolamine in intracellular membrane networks. FASEB J 29:568.34. https:\/\/doi.org\/10.1096\/FASEBJ.29.1_SUPPLEMENT.568.34","journal-title":"FASEB J"},{"key":"5849_CR55","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/J.BBADIS.2012.05.008","volume":"1822","author":"NE Braverman","year":"2012","unstructured":"Braverman NE, Moser AB (2012) Functions of plasmalogen lipids in health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1822:1442\u20131452. https:\/\/doi.org\/10.1016\/J.BBADIS.2012.05.008","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"5849_CR56","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.3233\/JAD-230061","volume":"93","author":"JK Blusztajn","year":"2023","unstructured":"Blusztajn JK, Slack BE (2023) Accelerated breakdown of phosphatidylcholine and phosphatidylethanolamine is a predominant brain metabolic defect in Alzheimer\u2019s disease. J Alzheimers Dis 93:1285. https:\/\/doi.org\/10.3233\/JAD-230061","journal-title":"J Alzheimers Dis"},{"key":"5849_CR57","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2019.00103","author":"JO Ojo","year":"2019","unstructured":"Ojo JO, Algamal M, Leary P et al (2019) Converging and differential brain phospholipid dysregulation in the pathogenesis of repetitive mild traumatic brain injury and Alzheimer\u2019s disease. Front Neurosci. https:\/\/doi.org\/10.3389\/FNINS.2019.00103","journal-title":"Front Neurosci"},{"key":"5849_CR58","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2018.00989","author":"AM Sabogal-Gu\u00e1queta","year":"2018","unstructured":"Sabogal-Gu\u00e1queta AM, Villamil-Ortiz JG, Arias-Londo\u00f1o JD, Cardona-G\u00f3mez GP (2018) Inverse phosphatidylcholine\/phosphatidylinositol levels as peripheral biomarkers and phosphatidylcholine\/lysophosphatidylethanolamine-phosphatidylserine as hippocampal indicator of postischemic cognitive impairment in rats. Front Neurosci. https:\/\/doi.org\/10.3389\/FNINS.2018.00989","journal-title":"Front Neurosci"},{"key":"5849_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROT.2025.E00525","author":"KC McGill Percy","year":"2025","unstructured":"McGill Percy KC, Liu Z, Qi X (2025) Mitochondrial dysfunction in Alzheimer\u2019s disease: guiding the path to targeted therapies. Neurotherapeutics. https:\/\/doi.org\/10.1016\/J.NEUROT.2025.E00525","journal-title":"Neurotherapeutics"},{"key":"5849_CR60","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/J.BBI.2023.08.027","volume":"114","author":"F Yasuno","year":"2023","unstructured":"Yasuno F, Kimura Y, Ogata A et al (2023) Neuroimaging biomarkers of glial activation for predicting the annual cognitive function decline in patients with Alzheimer\u2019s disease. Brain Behav Immun 114:214\u2013220. https:\/\/doi.org\/10.1016\/J.BBI.2023.08.027","journal-title":"Brain Behav Immun"},{"key":"5849_CR61","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/925050","author":"A Eckert","year":"2011","unstructured":"Eckert A, Pagani L (2011) Amyloid-beta interaction with mitochondria. Int J Alzheimers Dis. https:\/\/doi.org\/10.4061\/2011\/925050","journal-title":"Int J Alzheimers Dis"},{"key":"5849_CR62","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/S12035-015-9641-0","volume":"54","author":"T Ariga","year":"2017","unstructured":"Ariga T (2017) The pathogenic role of ganglioside metabolism in Alzheimer\u2019s disease-cholinergic neuron-specific gangliosides and neurogenesis. Mol Neurobiol 54:623\u2013638. https:\/\/doi.org\/10.1007\/S12035-015-9641-0","journal-title":"Mol Neurobiol"},{"key":"5849_CR63","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.plipres.2015.04.003","volume":"59","author":"PV Escrib\u00e1","year":"2015","unstructured":"Escrib\u00e1 PV, Busquets X, Inokuchi JI et al (2015) Membrane lipid therapy: modulation of the cell membrane composition and structure as a molecular base for drug discovery and new disease treatment. Prog Lipid Res 59:38\u201353. https:\/\/doi.org\/10.1016\/j.plipres.2015.04.003","journal-title":"Prog Lipid Res"},{"key":"5849_CR64","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1007\/S10495-015-1099-Z\/FIGURES\/5","volume":"20","author":"M Torres","year":"2015","unstructured":"Torres M, Marcilla-Etxenike A, Fiol-DeRoque MA et al (2015) The unfolded protein response in the therapeutic effect of hydroxy-DHA against Alzheimer\u2019s disease. Apoptosis 20:712\u2013724. https:\/\/doi.org\/10.1007\/S10495-015-1099-Z\/FIGURES\/5","journal-title":"Apoptosis"},{"key":"5849_CR65","doi-asserted-by":"publisher","DOI":"10.1186\/S13024-025-00803-6","author":"S He","year":"2025","unstructured":"He S, Xu Z, Han X (2025) Lipidome disruption in Alzheimer\u2019s disease brain: detection, pathological mechanisms, and therapeutic implications. Mol Neurodegener. https:\/\/doi.org\/10.1186\/S13024-025-00803-6","journal-title":"Mol Neurodegener"},{"key":"5849_CR66","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.brainres.2007.03.012","volume":"1151","author":"Y Uchiyama","year":"2007","unstructured":"Uchiyama Y, Maxson MM, Sawada T et al (2007) Phospholipid mediated plasticity in exocytosis observed in PC12 cells. Brain Res 1151:46\u201354. https:\/\/doi.org\/10.1016\/j.brainres.2007.03.012","journal-title":"Brain Res"},{"key":"5849_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/FNCEL.2022.988759","author":"P Roy","year":"2022","unstructured":"Roy P, Tomassoni D, Nittari G et al (2022) Effects of choline containing phospholipids on the neurovascular unit: a review. Front Cell Neurosci. https:\/\/doi.org\/10.3389\/FNCEL.2022.988759","journal-title":"Front Cell Neurosci"},{"key":"5849_CR68","doi-asserted-by":"publisher","first-page":"9411","DOI":"10.1002\/ANIE.201603178","volume":"55","author":"M Amaro","year":"2016","unstructured":"Amaro M, \u0160achl R, Aydogan G et al (2016) GM1 ganglioside inhibits \u03b2-amyloid oligomerization induced by sphingomyelin. Angew Chem Int Ed Engl 55:9411\u20139415. https:\/\/doi.org\/10.1002\/ANIE.201603178","journal-title":"Angew Chem Int Ed Engl"},{"key":"5849_CR69","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2020.572965","author":"S Sipione","year":"2020","unstructured":"Sipione S, Monyror J, Galleguillos D et al (2020) Gangliosides in the brain: physiology, pathophysiology and therapeutic applications. Front Neurosci. https:\/\/doi.org\/10.3389\/FNINS.2020.572965","journal-title":"Front Neurosci"},{"key":"5849_CR70","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/SYN.20747","volume":"64","author":"FMP Zitman","year":"2010","unstructured":"Zitman FMP, Todorov B, Furukawa K et al (2010) Total ganglioside ablation at mouse motor nerve terminals alters neurotransmitter release level. Synapse 64:335\u2013338. https:\/\/doi.org\/10.1002\/SYN.20747","journal-title":"Synapse"},{"key":"5849_CR71","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.brainresbull.2019.01.002","volume":"146","author":"CB Pointer","year":"2019","unstructured":"Pointer CB, Wenzel TJ, Klegeris A (2019) Extracellular cardiolipin regulates select immune functions of microglia and microglia-like cells. Brain Res Bull 146:153\u2013163. https:\/\/doi.org\/10.1016\/j.brainresbull.2019.01.002","journal-title":"Brain Res Bull"},{"key":"5849_CR72","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1016\/j.bbamem.2009.04.020","volume":"1788","author":"SM Claypool","year":"2009","unstructured":"Claypool SM (2009) Cardiolipin, a critical determinant of mitochondrial carrier protein assembly and function. Biochimica et Biophysica Acta (BBA) - Biomembranes 1788:2059\u20132068. https:\/\/doi.org\/10.1016\/j.bbamem.2009.04.020","journal-title":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},{"key":"5849_CR73","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1194\/JLR.M800319-JLR200","volume":"49","author":"MA Kiebish","year":"2008","unstructured":"Kiebish MA, Han X, Cheng H et al (2008) Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. J Lipid Res 49:2545\u20132556. https:\/\/doi.org\/10.1194\/JLR.M800319-JLR200","journal-title":"J Lipid Res"},{"key":"5849_CR74","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.ceca.2009.03.012","volume":"45","author":"G Paradies","year":"2009","unstructured":"Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2009) Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease. Cell Calcium 45:643\u2013650. https:\/\/doi.org\/10.1016\/j.ceca.2009.03.012","journal-title":"Cell Calcium"},{"key":"5849_CR75","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.neuint.2005.12.018","volume":"49","author":"T Sen","year":"2006","unstructured":"Sen T, Sen N, Tripathi G et al (2006) Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria. Neurochem Int 49:20\u201327. https:\/\/doi.org\/10.1016\/j.neuint.2005.12.018","journal-title":"Neurochem Int"},{"key":"5849_CR76","doi-asserted-by":"publisher","DOI":"10.3389\/FPHYS.2022.864263","author":"S Vegas-Su\u00e1rez","year":"2022","unstructured":"Vegas-Su\u00e1rez S, Sim\u00f3n J, Mart\u00ednez-Chantar ML, Moratalla R (2022) Metabolic diffusion in neuropathologies: the relevance of brain-liver axis. Front Physiol. https:\/\/doi.org\/10.3389\/FPHYS.2022.864263","journal-title":"Front Physiol"},{"key":"5849_CR77","doi-asserted-by":"publisher","DOI":"10.1186\/S12944-025-02455-3","author":"Z Wang","year":"2025","unstructured":"Wang Z, Yin Z, Sun G et al (2025) Genetic evidence for the liver-brain axis: lipid metabolism and neurodegenerative disease risk. Lipids Health Dis. https:\/\/doi.org\/10.1186\/S12944-025-02455-3","journal-title":"Lipids Health Dis"},{"key":"5849_CR78","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.4103\/NRR.NRR-D-23-01770","volume":"20","author":"E Asimakidou","year":"2025","unstructured":"Asimakidou E, Saipuljumri EN, Lo CH, Zeng J (2025) Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration. Neural Regen Res 20:1069\u20131076. https:\/\/doi.org\/10.4103\/NRR.NRR-D-23-01770","journal-title":"Neural Regen Res"},{"key":"5849_CR79","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-018-30487-6","author":"A Ng","year":"2018","unstructured":"Ng A, Tam WW, Zhang MW et al (2018) IL-1\u03b2, IL-6, TNF- \u03b1 and CRP in elderly patients with depression or Alzheimer\u2019s disease: systematic review and meta-analysis. Sci Rep. https:\/\/doi.org\/10.1038\/S41598-018-30487-6","journal-title":"Sci Rep"},{"key":"5849_CR80","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2021.796867","author":"J Xie","year":"2022","unstructured":"Xie J, Van Hoecke L, Vandenbroucke RE (2022) The impact of systemic inflammation on Alzheimer\u2019s disease pathology. Front Immunol. https:\/\/doi.org\/10.3389\/FIMMU.2021.796867","journal-title":"Front Immunol"},{"key":"5849_CR81","doi-asserted-by":"publisher","first-page":"819","DOI":"10.3233\/JAD-160925","volume":"60","author":"MM Mielke","year":"2017","unstructured":"Mielke MM, Haughey NJ, Han D et al (2017) 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. J Alzheimers Dis 60:819\u2013828. https:\/\/doi.org\/10.3233\/JAD-160925","journal-title":"J Alzheimers Dis"},{"key":"5849_CR82","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.14336\/AD.2023.0221","volume":"14","author":"F Dakterzada","year":"2023","unstructured":"Dakterzada F, Jov\u00e9 M, Huerto R et al (2023) Changes in plasma neutral and ether-linked lipids are associated with the pathology and progression of Alzheimer\u2019s disease. Aging Dis 14:1728\u20131738. https:\/\/doi.org\/10.14336\/AD.2023.0221","journal-title":"Aging Dis"},{"key":"5849_CR83","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/CDD.2014.128","volume":"22","author":"T Yabu","year":"2015","unstructured":"Yabu T, Shiba H, Shibasaki Y et al (2015) Stress-induced ceramide generation and apoptosis via the phosphorylation and activation of nSMase1 by JNK signaling. Cell Death Differ 22:258\u2013273. https:\/\/doi.org\/10.1038\/CDD.2014.128","journal-title":"Cell Death Differ"},{"key":"5849_CR84","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-019-09654-4","author":"S Dadsena","year":"2019","unstructured":"Dadsena S, Bockelmann S, Mina JGM et al (2019) Ceramides bind VDAC2 to trigger mitochondrial apoptosis. Nat Commun. https:\/\/doi.org\/10.1038\/S41467-019-09654-4","journal-title":"Nat Commun"},{"key":"5849_CR85","doi-asserted-by":"publisher","DOI":"10.1038\/S42003-024-07231-0","author":"JJ McInnis","year":"2024","unstructured":"McInnis JJ, Sood D, Guo L et al (2024) Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity. Commun Biol. https:\/\/doi.org\/10.1038\/S42003-024-07231-0","journal-title":"Commun Biol"},{"key":"5849_CR86","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1111\/JNC.15759","volume":"164","author":"S Bernal-Vega","year":"2023","unstructured":"Bernal-Vega S, Garc\u00eda-Ju\u00e1rez M, Camacho-Morales A (2023) Contribution of ceramides metabolism in psychiatric disorders. J Neurochem 164:708\u2013724. https:\/\/doi.org\/10.1111\/JNC.15759","journal-title":"J Neurochem"},{"key":"5849_CR87","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/S12017-010-8121-Y","volume":"12","author":"MM Mielke","year":"2010","unstructured":"Mielke MM, Lyketsos CG (2010) Alterations of the sphingolipid pathway in Alzheimer\u2019s disease: new biomarkers and treatment targets? Neuromolecular Med 12:331\u2013340. https:\/\/doi.org\/10.1007\/S12017-010-8121-Y","journal-title":"Neuromolecular Med"},{"key":"5849_CR88","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/B978-0-12-819641-0.00146-8","volume":"1\u20133","author":"JL Johnson","year":"2022","unstructured":"Johnson JL, Johnson LA (2022) Homeostasis of lipid metabolism in disorders of the brain. Encyclopedia of Behavioral Neuroscience: Volumes 1\u20133. Second edition 1\u20133:372\u2013382. https:\/\/doi.org\/10.1016\/B978-0-12-819641-0.00146-8","journal-title":"Second edition"},{"key":"5849_CR89","doi-asserted-by":"publisher","DOI":"10.1186\/ALZRT103","author":"PL Wood","year":"2012","unstructured":"Wood PL (2012) Lipidomics of Alzheimer\u2019s disease: current status. Alzheimers Res Ther. https:\/\/doi.org\/10.1186\/ALZRT103","journal-title":"Alzheimers Res Ther"},{"key":"5849_CR90","doi-asserted-by":"publisher","DOI":"10.1016\/J.PLIPRES.2023.101223","author":"L Ferr\u00e9-Gonz\u00e1lez","year":"2023","unstructured":"Ferr\u00e9-Gonz\u00e1lez L, Lloret A, Ch\u00e1fer-Peric\u00e1s C (2023) Systematic review of brain and blood lipidomics in Alzheimer\u2019s disease mouse models. Prog Lipid Res. https:\/\/doi.org\/10.1016\/J.PLIPRES.2023.101223","journal-title":"Prog Lipid Res"},{"key":"5849_CR91","doi-asserted-by":"publisher","DOI":"10.7554\/ELIFE.90633","volume":"13","author":"A Granzotto","year":"2024","unstructured":"Granzotto A, Vissel B, Sensi SL (2024) Lost in translation: inconvenient truths on the utility of mouse models in Alzheimer\u2019s disease research. Elife 13:e90633. https:\/\/doi.org\/10.7554\/ELIFE.90633","journal-title":"Elife"},{"issue":"10","key":"5849_CR92","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/S13238-022-00912-8","volume":"2022","author":"P Yin","year":"2022","unstructured":"Yin P, Li S, Li XJ, Yang W (2022) New pathogenic insights from large animal models of neurodegenerative diseases. Protein Cell 2022(10):707\u2013720. https:\/\/doi.org\/10.1007\/S13238-022-00912-8","journal-title":"Protein Cell"},{"key":"5849_CR93","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-021-01054-y","author":"S Forner","year":"2021","unstructured":"Forner S, Kawauchi S, Balderrama-Gutierrez G et al (2021) Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer\u2019s disease. Sci Data. https:\/\/doi.org\/10.1038\/s41597-021-01054-y","journal-title":"Sci Data"},{"key":"5849_CR94","doi-asserted-by":"publisher","DOI":"10.3389\/FNANA.2021.690168","volume":"15","author":"NY Seo","year":"2021","unstructured":"Seo NY, Kim GH, Noh JE et al (2021) Selective regional loss of cortical synapses lacking presynaptic mitochondria in the 5xFAD mouse model. Front Neuroanat 15:690168. https:\/\/doi.org\/10.3389\/FNANA.2021.690168","journal-title":"Front Neuroanat"},{"key":"5849_CR95","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/J.NEUROSCIENCE.2013.09.016","volume":"254","author":"Y Buskila","year":"2013","unstructured":"Buskila Y, Crowe SE, Ellis-Davies GCR (2013) Synaptic deficits in layer 5 neurons precede overt structural decay in 5xFAD mice. Neuroscience 254:152. https:\/\/doi.org\/10.1016\/J.NEUROSCIENCE.2013.09.016","journal-title":"Neuroscience"},{"key":"5849_CR96","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.3233\/JAD-141002","volume":"43","author":"VF Monteiro-Cardoso","year":"2014","unstructured":"Monteiro-Cardoso VF, Oliveira MM, Melo T et al (2014) Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer\u2019s disease. J Alzheimers Dis 43:1375\u20131392. https:\/\/doi.org\/10.3233\/JAD-141002","journal-title":"J Alzheimers Dis"},{"key":"5849_CR97","doi-asserted-by":"publisher","DOI":"10.1038\/S12276-019-0326-Z","author":"DK Kim","year":"2019","unstructured":"Kim DK, Han D, Park J et al (2019) Deep proteome profiling of the hippocampus in the 5XFAD mouse model reveals biological process alterations and a novel biomarker of Alzheimer\u2019s disease. Exp Mol Med. https:\/\/doi.org\/10.1038\/S12276-019-0326-Z","journal-title":"Exp Mol Med"},{"key":"5849_CR98","doi-asserted-by":"publisher","DOI":"10.1016\/J.ISCI.2024.108800","author":"JPS Marshall","year":"2024","unstructured":"Marshall JPS, Huynh K, Lancaster GI et al (2024) Behavioral, metabolic, and lipidomic characterization of the 5xFADxTg30 mouse model of Alzheimer\u2019s disease. iScience. https:\/\/doi.org\/10.1016\/J.ISCI.2024.108800","journal-title":"iScience"},{"key":"5849_CR99","doi-asserted-by":"publisher","first-page":"3537","DOI":"10.1038\/S41380-024-02598-2","volume":"29","author":"O T\u00fcscher","year":"2024","unstructured":"T\u00fcscher O, Muthuraman M, Horstmann JP et al (2024) Altered cortical synaptic lipid signaling leads to intermediate phenotypes of mental disorders. Mol Psychiatry 29:3537\u20133552. https:\/\/doi.org\/10.1038\/S41380-024-02598-2","journal-title":"Mol Psychiatry"},{"key":"5849_CR100","doi-asserted-by":"publisher","DOI":"10.1038\/S41598-023-41897-6","author":"DC Shippy","year":"2023","unstructured":"Shippy DC, Ulland TK (2023) Lipid metabolism transcriptomics of murine microglia in Alzheimer\u2019s disease and neuroinflammation. Sci Rep. https:\/\/doi.org\/10.1038\/S41598-023-41897-6","journal-title":"Sci Rep"},{"key":"5849_CR101","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1038\/S41593-024-01740-1","volume":"27","author":"LD Goodman","year":"2024","unstructured":"Goodman LD, Ralhan I, Li X et al (2024) Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress. Nat Neurosci 27:1918\u20131933. https:\/\/doi.org\/10.1038\/S41593-024-01740-1","journal-title":"Nat Neurosci"},{"key":"5849_CR102","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/ELPS.201400450","volume":"36","author":"R Gonz\u00e1lez-Dom\u00ednguez","year":"2015","unstructured":"Gonz\u00e1lez-Dom\u00ednguez R, Garc\u00eda-Barrera T, Vitorica J, G\u00f3mez-Ariza JL (2015) Metabolomics reveals significant impairments in the immune system of the APP\/PS1 transgenic mice of Alzheimer\u2019s disease. Electrophoresis 36:577\u2013587. https:\/\/doi.org\/10.1002\/ELPS.201400450","journal-title":"Electrophoresis"},{"key":"5849_CR103","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3233\/JAD-221175","volume":"94","author":"JDA Rudge","year":"2023","unstructured":"Rudge JDA (2023) The lipid invasion model: growing evidence for this new explanation of Alzheimer\u2019s disease. J Alzheimers Dis 94:457. https:\/\/doi.org\/10.3233\/JAD-221175","journal-title":"J Alzheimers Dis"},{"key":"5849_CR104","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2021.630502","author":"MA Husain","year":"2021","unstructured":"Husain MA, Laurent B, Plourde M (2021) APOE and Alzheimer\u2019s disease: from lipid transport to physiopathology and therapeutics. Front Neurosci. https:\/\/doi.org\/10.3389\/FNINS.2021.630502","journal-title":"Front Neurosci"},{"key":"5849_CR105","doi-asserted-by":"publisher","unstructured":"Haney MS, P\u00e1lovics R, Munson CN et al (2024) APOE4\/4 is linked to damaging lipid droplets in Alzheimer\u2019s disease\u00a0microglia. Nature. https:\/\/doi.org\/10.1038\/s41586-024-07185-7","DOI":"10.1038\/s41586-024-07185-7"},{"key":"5849_CR106","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/2211-5463.13661","volume":"14","author":"N Kawade","year":"2023","unstructured":"Kawade N, Yamanaka K (2023) Novel insights into brain lipid metabolism in Alzheimer\u2019s disease: oligodendrocytes and white matter abnormalities. FEBS Open Bio 14:194. https:\/\/doi.org\/10.1002\/2211-5463.13661","journal-title":"FEBS Open Bio"},{"key":"5849_CR107","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3233\/ADR-210299","volume":"6","author":"JDA Rudge","year":"2022","unstructured":"Rudge JDA (2022) A new hypothesis for Alzheimer\u2019s disease: the lipid invasion model. J Alzheimers Dis Rep 6:129. https:\/\/doi.org\/10.3233\/ADR-210299","journal-title":"J Alzheimers Dis Rep"},{"key":"5849_CR108","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1016\/J.BBAMEM.2013.12.016","volume":"1838","author":"M Torres","year":"2014","unstructured":"Torres M, Price SL, Fiol-Deroque MA et al (2014) Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimer\u2019s disease. Biochimica et Biophysica Acta (BBA) - Biomembranes 1838:1680\u20131692. https:\/\/doi.org\/10.1016\/J.BBAMEM.2013.12.016","journal-title":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},{"issue":"1","key":"5849_CR109","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/S41398-025-03321-7","volume":"15","author":"H Suloh","year":"2025","unstructured":"Suloh H, Ojha SK, Kartawy M et al (2025) Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer\u2019s disease mouse models. Transl Psychiatry 15(1):1\u201311. https:\/\/doi.org\/10.1038\/S41398-025-03321-7","journal-title":"Transl Psychiatry"},{"key":"5849_CR110","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04237-y","author":"JV Andersen","year":"2021","unstructured":"Andersen JV, Skotte NH, Christensen SK et al (2021) Hippocampal disruptions of synaptic and astrocyte metabolism are primary events of early amyloid pathology in the 5xFAD mouse model of Alzheimer\u2019s disease. Cell Death Dis. https:\/\/doi.org\/10.1038\/s41419-021-04237-y","journal-title":"Cell Death Dis"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05849-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-05849-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05849-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:51:41Z","timestamp":1776109901000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-05849-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":110,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5849"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-05849-1","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"7 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the experimental procedures involving animals were carried out following the animal welfare guidelines of the European Union (86\/609\/EEC) and with the authorization of the Institutional Committee for Animal Research at the University of the Balearic Islands (CEEA-UIB) and the regional government of the Balearic Islands (GOIB). Human samples were obtained from national biobanks under authorization by the Committee for Ethical Research of the Balearic Islands (CEI-IB) dependent of GOIB.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"561"}}