{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:26:13Z","timestamp":1792801573715,"version":"4.5.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["ZZ14-FL-005"],"award-info":[{"award-number":["ZZ14-FL-005"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82174210"],"award-info":[{"award-number":["82174210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"China Academy of Chinese Medical Sciences CACMS Innovation Fund","award":["CI2021A01306"],"award-info":[{"award-number":["CI2021A01306"]}],"id":[{"id":"https:\/\/ror.org\/042pgcv68","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Scientific and technological innovation project of China Academy of Chinese Medical Sciences","award":["CI2021B003"],"award-info":[{"award-number":["CI2021B003"]}],"id":[{"id":"https:\/\/ror.org\/042pgcv68","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lipid metabolism changes occur\u00a0in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein\u2013protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>60 lipid metabolic genes differentially expressed in early AD patients\u2019 cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40001-024-01730-w","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T08:01:59Z","timestamp":1711353719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cortical lipid metabolic pathway alteration of early Alzheimer\u2019s disease and candidate drugs screen"],"prefix":"10.1186","volume":"29","author":[{"given":"Linshuang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxue","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixia","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"1730_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nrd2896","volume":"9","author":"M Citron","year":"2010","unstructured":"Citron M. Alzheimer\u2019s disease: strategies for disease modification. Nat Rev Drug Discov. 2010;9:387\u201398. https:\/\/doi.org\/10.1038\/nrd2896.","journal-title":"Nat Rev Drug Discov"},{"key":"1730_CR2","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1038\/d41586-018-05717-6","volume":"559","author":"R Hodson","year":"2018","unstructured":"Hodson R. Alzheimer\u2019s disease. Nature. 2018;559:S1. https:\/\/doi.org\/10.1038\/d41586-018-05717-6.","journal-title":"Nature"},{"key":"1730_CR3","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.bbi.2019.05.009","volume":"80","author":"H Patel","year":"2019","unstructured":"Patel H, et al. Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer brains. Brain Behav Immun. 2019;80:644\u201356. https:\/\/doi.org\/10.1016\/j.bbi.2019.05.009.","journal-title":"Brain Behav Immun"},{"key":"1730_CR4","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3233\/JAD-2010-1374","volume":"20","author":"MA Daulatzai","year":"2010","unstructured":"Daulatzai MA. Early stages of pathogenesis in memory impairment during normal senescence and Alzheimer\u2019s disease. J Alzheimers Dis. 2010;20:355\u201367. https:\/\/doi.org\/10.3233\/JAD-2010-1374.","journal-title":"J Alzheimers Dis"},{"key":"1730_CR5","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.3233\/JAD-200892","volume":"79","author":"JH Park","year":"2021","unstructured":"Park JH, Lee SA. The fragility of temporal memory in Alzheimer\u2019s disease. J Alzheimers Dis. 2021;79:1631\u201346. https:\/\/doi.org\/10.3233\/JAD-200892.","journal-title":"J Alzheimers Dis"},{"key":"1730_CR6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12883-017-1008-x","volume":"18","author":"L Feng","year":"2018","unstructured":"Feng L, et al. Plasma long non-coding RNA BACE1 as a novel biomarker for diagnosis of Alzheimer disease. BMC Neurol. 2018;18:4. https:\/\/doi.org\/10.1186\/s12883-017-1008-x.","journal-title":"BMC Neurol"},{"key":"1730_CR7","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1073\/pnas.0308512100","volume":"101","author":"EM Blalock","year":"2004","unstructured":"Blalock EM, et al. Incipient Alzheimer\u2019s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA. 2004;101:2173\u20138. https:\/\/doi.org\/10.1073\/pnas.0308512100.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1730_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105143","volume":"149","author":"KM Ooi","year":"2021","unstructured":"Ooi KM, Vacy K, Boon WC. Fatty acids and beyond: age and Alzheimer\u2019s disease related changes in lipids reveal the neuro-nutraceutical potential of lipids in cognition. Neurochem Int. 2021;149: 105143. https:\/\/doi.org\/10.1016\/j.neuint.2021.105143.","journal-title":"Neurochem Int"},{"key":"1730_CR9","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.3390\/cells10102591","volume":"10","author":"S Akyol","year":"2021","unstructured":"Akyol S, et al. Lipid profiling of Alzheimer\u2019s disease brain highlights enrichment in glycerol(phospho)lipid, and sphingolipid metabolism. Cells. 2021;10:2591. https:\/\/doi.org\/10.3390\/cells10102591.","journal-title":"Cells"},{"key":"1730_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2021.105072","volume":"236","author":"S Garcia-Vinuales","year":"2021","unstructured":"Garcia-Vinuales S, et al. The interplay between lipid and Abeta amyloid homeostasis in Alzheimer\u2019s disease: risk factors and therapeutic opportunities. Chem Phys Lipids. 2021;236: 105072. https:\/\/doi.org\/10.1016\/j.chemphyslip.2021.105072.","journal-title":"Chem Phys Lipids"},{"key":"1730_CR11","doi-asserted-by":"publisher","first-page":"226","DOI":"10.3390\/membranes10090226","volume":"10","author":"V Rudajev","year":"2020","unstructured":"Rudajev V, Novotny J. The role of lipid environment in ganglioside GM1-induced amyloid beta aggregation. Membranes (Basel). 2020;10:226. https:\/\/doi.org\/10.3390\/membranes10090226.","journal-title":"Membranes (Basel)"},{"key":"1730_CR12","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.3390\/ijms22041984","volume":"22","author":"J Poejo","year":"2021","unstructured":"Poejo J, Salazar J, Mata AM, Gutierrez-Merino C. Binding of amyloid beta(1\u201342)-calmodulin complexes to plasma membrane lipid rafts in cerebellar granule neurons alters resting cytosolic calcium homeostasis. Int J Mol Sci. 2021;22:1984. https:\/\/doi.org\/10.3390\/ijms22041984.","journal-title":"Int J Mol Sci"},{"key":"1730_CR13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/978-1-4020-8831-5_9","volume":"49","author":"RM Adibhatla","year":"2008","unstructured":"Adibhatla RM, Hatcher JF. Altered lipid metabolism in brain injury and disorders. Subcell Biochem. 2008;49:241\u201368. https:\/\/doi.org\/10.1007\/978-1-4020-8831-5_9.","journal-title":"Subcell Biochem"},{"key":"1730_CR14","doi-asserted-by":"publisher","first-page":"5243453","DOI":"10.1155\/2020\/5243453","volume":"2020","author":"M Yi","year":"2020","unstructured":"Yi M, et al. Integrated metabolomic and lipidomic analysis reveals the neuroprotective mechanisms of Bushen Tiansui formula in an abeta1-42-induced rat model of Alzheimer\u2019s disease. Oxid Med Cell Longev. 2020;2020:5243453. https:\/\/doi.org\/10.1155\/2020\/5243453.","journal-title":"Oxid Med Cell Longev"},{"key":"1730_CR15","doi-asserted-by":"publisher","first-page":"10117","DOI":"10.1523\/JNEUROSCI.5268-11.2012","volume":"32","author":"S Mandrekar-Colucci","year":"2012","unstructured":"Mandrekar-Colucci S, Karlo JC, Landreth GE. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-gamma-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer\u2019s disease. J Neurosci. 2012;32:10117\u201328. https:\/\/doi.org\/10.1523\/JNEUROSCI.5268-11.2012.","journal-title":"J Neurosci"},{"key":"1730_CR16","doi-asserted-by":"publisher","first-page":"D520","DOI":"10.1093\/nar\/gky949","volume":"47","author":"wwPDB Consortium","year":"2019","unstructured":"wwPDB Consortium. Protein Data Bank: the single global archive for 3D macromolecular structure data. Nucleic Acids Res. 2019;47:D520\u20138. https:\/\/doi.org\/10.1093\/nar\/gky949.","journal-title":"Nucleic Acids Res"},{"key":"1730_CR17","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"J Jumper","year":"2021","unstructured":"Jumper J, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583\u20139. https:\/\/doi.org\/10.1038\/s41586-021-03819-2.","journal-title":"Nature"},{"key":"1730_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105920","volume":"26","author":"V Scardino","year":"2023","unstructured":"Scardino V, Di Filippo JI, Cavasotto CN. How good are AlphaFold models for docking-based virtual screening? iScience. 2023;26: 105920. https:\/\/doi.org\/10.1016\/j.isci.2022.105920.","journal-title":"iScience"},{"key":"1730_CR19","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.nbd.2005.09.004","volume":"21","author":"L Emilsson","year":"2006","unstructured":"Emilsson L, Saetre P, Jazin E. Alzheimer\u2019s disease: mRNA expression profiles of multiple patients show alterations of genes involved with calcium signaling. Neurobiol Dis. 2006;21:618\u201325. https:\/\/doi.org\/10.1016\/j.nbd.2005.09.004.","journal-title":"Neurobiol Dis"},{"key":"1730_CR20","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.924263","volume":"26","author":"X Wang","year":"2020","unstructured":"Wang X, Wang L. Screening and identification of potential peripheral blood biomarkers for Alzheimer\u2019s disease based on bioinformatics analysis. Med Sci Monit Int Med J Exp Clin Res. 2020;26: e924263. https:\/\/doi.org\/10.12659\/MSM.924263.","journal-title":"Med Sci Monit Int Med J Exp Clin Res"},{"issue":"Suppl 4","key":"1730_CR21","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1752-0509-8-S4-S11","volume":"8","author":"CH Chin","year":"2014","unstructured":"Chin CH, et al. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(Suppl 4):S11. https:\/\/doi.org\/10.1186\/1752-0509-8-S4-S11.","journal-title":"BMC Syst Biol"},{"key":"1730_CR22","doi-asserted-by":"publisher","first-page":"D1138","DOI":"10.1093\/nar\/gkaa891","volume":"49","author":"AP Davis","year":"2021","unstructured":"Davis AP, et al. Comparative toxicogenomics database (CTD): update 2021. Nucleic Acids Res. 2021;49:D1138\u201343. https:\/\/doi.org\/10.1093\/nar\/gkaa891.","journal-title":"Nucleic Acids Res"},{"key":"1730_CR23","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1016\/j.neurobiolaging.2012.12.026","volume":"34","author":"A Antonell","year":"2013","unstructured":"Antonell A, et al. A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimer\u2019s disease. Neurobiol Aging. 2013;34:1772\u20138. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2012.12.026.","journal-title":"Neurobiol Aging"},{"key":"1730_CR24","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12944-020-01367-8","volume":"19","author":"M Dey","year":"2020","unstructured":"Dey M, Gunn-Moore FJ, Platt B, Smith TK. Brain region-specific lipid alterations in the PLB4 hBACE1 knock-in mouse model of Alzheimer\u2019s disease. Lipids Health Dis. 2020;19:201. https:\/\/doi.org\/10.1186\/s12944-020-01367-8.","journal-title":"Lipids Health Dis"},{"key":"1730_CR25","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/glia.23558","volume":"67","author":"L Zhong","year":"2019","unstructured":"Zhong L, et al. Lipid transporter Spns2 promotes microglia pro-inflammatory activation in response to amyloid-beta peptide. Glia. 2019;67:498\u2013511. https:\/\/doi.org\/10.1002\/glia.23558.","journal-title":"Glia"},{"key":"1730_CR26","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/s41557-018-0031-x","volume":"10","author":"J Habchi","year":"2018","unstructured":"Habchi J, et al. Cholesterol catalyses Abeta42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes. Nat Chem. 2018;10:673\u201383. https:\/\/doi.org\/10.1038\/s41557-018-0031-x.","journal-title":"Nat Chem"},{"key":"1730_CR27","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack CR Jr, et al. NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 2018;14:535\u201362. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018.","journal-title":"Alzheimers Dement"},{"key":"1730_CR28","doi-asserted-by":"publisher","first-page":"92","DOI":"10.4103\/1673-5374.125335","volume":"9","author":"X Zhou","year":"2014","unstructured":"Zhou X, et al. Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer\u2019s disease. Neural Regen Res. 2014;9:92\u2013100. https:\/\/doi.org\/10.4103\/1673-5374.125335.","journal-title":"Neural Regen Res"},{"key":"1730_CR29","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3233\/JAD-171054","volume":"63","author":"TA Couttas","year":"2018","unstructured":"Couttas TA, et al. Age-dependent changes to sphingolipid balance in the human hippocampus are gender-specific and may sensitize to neurodegeneration. J Alzheimers Dis. 2018;63:503\u201314. https:\/\/doi.org\/10.3233\/JAD-171054.","journal-title":"J Alzheimers Dis"},{"key":"1730_CR30","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1749-6632.2000.tb05564.x","volume":"924","author":"J Poirier","year":"2000","unstructured":"Poirier J. Apolipoprotein E and Alzheimer\u2019s disease. A role in amyloid catabolism. Ann N Y Acad Sci. 2000;924:81\u201390. https:\/\/doi.org\/10.1111\/j.1749-6632.2000.tb05564.x.","journal-title":"Ann N Y Acad Sci"},{"key":"1730_CR31","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1002\/acn3.51153","volume":"7","author":"H Hu","year":"2020","unstructured":"Hu H, et al. Association of serum apolipoprotein B with cerebrospinal fluid biomarkers of Alzheimer\u2019s pathology. Ann Clin Transl Neurol. 2020;7:1766\u201378. https:\/\/doi.org\/10.1002\/acn3.51153.","journal-title":"Ann Clin Transl Neurol"},{"key":"1730_CR32","doi-asserted-by":"publisher","first-page":"11883","DOI":"10.1096\/fj.201903128RR","volume":"34","author":"NM Stoye","year":"2020","unstructured":"Stoye NM, Dos Santos Guilherme M, Endres K. Alzheimer\u2019s disease in the gut-major changes in the gut of 5xFAD model mice with ApoA1 as potential key player. FASEB J. 2020;34:11883\u201399. https:\/\/doi.org\/10.1096\/fj.201903128RR.","journal-title":"FASEB J"},{"key":"1730_CR33","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13195-019-0497-9","volume":"11","author":"EB Button","year":"2019","unstructured":"Button EB, et al. ApoA-I deficiency increases cortical amyloid deposition, cerebral amyloid angiopathy, cortical and hippocampal astrogliosis, and amyloid-associated astrocyte reactivity in APP\/PS1 mice. Alzheimers Res Ther. 2019;11:44. https:\/\/doi.org\/10.1186\/s13195-019-0497-9.","journal-title":"Alzheimers Res Ther"},{"key":"1730_CR34","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1111\/nan.12556","volume":"45","author":"L Contu","year":"2019","unstructured":"Contu L, Carare RO, Hawkes CA. Knockout of apolipoprotein A-I decreases parenchymal and vascular beta-amyloid pathology in the Tg2576 mouse model of Alzheimer\u2019s disease. Neuropathol Appl Neurobiol. 2019;45:698\u2013714. https:\/\/doi.org\/10.1111\/nan.12556.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1730_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2004.09.001","volume":"26","author":"RK Gopalraj","year":"2005","unstructured":"Gopalraj RK, et al. Genetic association of low density lipoprotein receptor and Alzheimer\u2019s disease. Neurobiol Aging. 2005;26:1\u20137. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2004.09.001.","journal-title":"Neurobiol Aging"},{"key":"1730_CR36","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s11064-006-9084-0","volume":"31","author":"Y Abdulkarim","year":"2006","unstructured":"Abdulkarim Y, Hameed Z. Is the LDL receptor involved in cortical amyloid protein clearance? Neurochem Res. 2006;31:839\u201347. https:\/\/doi.org\/10.1007\/s11064-006-9084-0.","journal-title":"Neurochem Res"},{"key":"1730_CR37","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/j.neurobiolaging.2005.09.011","volume":"27","author":"D Cao","year":"2006","unstructured":"Cao D, Fukuchi K, Wan H, Kim H, Li L. Lack of LDL receptor aggravates learning deficits and amyloid deposits in Alzheimer transgenic mice. Neurobiol Aging. 2006;27:1632\u201343. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2005.09.011.","journal-title":"Neurobiol Aging"},{"key":"1730_CR38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009406","volume":"17","author":"AG Nackenoff","year":"2021","unstructured":"Nackenoff AG, et al. PLD3 is a neuronal lysosomal phospholipase D associated with beta-amyloid plaques and cognitive function in Alzheimer\u2019s disease. PLoS Genet. 2021;17: e1009406. https:\/\/doi.org\/10.1371\/journal.pgen.1009406.","journal-title":"PLoS Genet"},{"key":"1730_CR39","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3389\/fnins.2019.00116","volume":"13","author":"M Tan","year":"2019","unstructured":"Tan M, et al. PLD3 rare variants identified in late-onset Alzheimer\u2019s disease affect amyloid-beta levels in cellular model. Front Neurosci. 2019;13:116. https:\/\/doi.org\/10.3389\/fnins.2019.00116.","journal-title":"Front Neurosci"},{"key":"1730_CR40","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1007\/s00018-018-2752-9","volume":"75","author":"AS Mukadam","year":"2018","unstructured":"Mukadam AS, Breusegem SY, Seaman MNJ. Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing. Cell Mol Life Sci. 2018;75:2613\u201325. https:\/\/doi.org\/10.1007\/s00018-018-2752-9.","journal-title":"Cell Mol Life Sci"},{"key":"1730_CR41","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/nature12825","volume":"505","author":"C Cruchaga","year":"2014","unstructured":"Cruchaga C, et al. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer\u2019s disease. Nature. 2014;505:550\u20134. https:\/\/doi.org\/10.1038\/nature12825.","journal-title":"Nature"},{"key":"1730_CR42","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1038\/nature21030","volume":"541","author":"P Fazzari","year":"2017","unstructured":"Fazzari P, et al. PLD3 gene and processing of APP. Nature. 2017;541:E1\u20132. https:\/\/doi.org\/10.1038\/nature21030.","journal-title":"Nature"},{"key":"1730_CR43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13024-016-0099-y","volume":"11","author":"Y Fu","year":"2016","unstructured":"Fu Y, et al. Apolipoprotein E lipoprotein particles inhibit amyloid-beta uptake through cell surface heparan sulphate proteoglycan. Mol Neurodegener. 2016;11:37. https:\/\/doi.org\/10.1186\/s13024-016-0099-y.","journal-title":"Mol Neurodegener"},{"key":"1730_CR44","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1194\/jlr.R075796","volume":"58","author":"M Shinohara","year":"2017","unstructured":"Shinohara M, Tachibana M, Kanekiyo T, Bu G. Role of LRP1 in the pathogenesis of Alzheimer\u2019s disease: evidence from clinical and preclinical studies. J Lipid Res. 2017;58:1267\u201381. https:\/\/doi.org\/10.1194\/jlr.R075796.","journal-title":"J Lipid Res"},{"key":"1730_CR45","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.ajpath.2019.04.010","volume":"189","author":"T Bilousova","year":"2019","unstructured":"Bilousova T, et al. Apolipoprotein E\/amyloid-beta complex accumulates in Alzheimer disease cortical synapses via apolipoprotein E receptors and is enhanced by APOE4. Am J Pathol. 2019;189:1621\u201336. https:\/\/doi.org\/10.1016\/j.ajpath.2019.04.010.","journal-title":"Am J Pathol"},{"key":"1730_CR46","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neulet.2012.07.065","volume":"525","author":"WA Ruzali","year":"2012","unstructured":"Ruzali WA, Kehoe PG, Love S. LRP1 expression in cerebral cortex, choroid plexus and meningeal blood vessels: relationship to cerebral amyloid angiopathy and APOE status. Neurosci Lett. 2012;525:123\u20138. https:\/\/doi.org\/10.1016\/j.neulet.2012.07.065.","journal-title":"Neurosci Lett"},{"issue":"628","key":"1730_CR47","doi-asserted-by":"publisher","first-page":"e621","DOI":"10.1016\/j.neurobiolaging.2011.04.010","volume":"33","author":"A Akram","year":"2012","unstructured":"Akram A, Schmeidler J, Katsel P, Hof PR, Haroutunian V. Association of ApoE and LRP mRNA levels with dementia and AD neuropathology. Neurobiol Aging. 2012;33(628):e621-628.e614. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2011.04.010.","journal-title":"Neurobiol Aging"},{"key":"1730_CR48","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1111\/j.1471-4159.2010.07033.x","volume":"116","author":"JC Lee","year":"2011","unstructured":"Lee JC, Simonyi A, Sun AY, Sun GY. Phospholipases A2 and neural membrane dynamics: implications for Alzheimer\u2019s disease. J Neurochem. 2011;116:813\u20139. https:\/\/doi.org\/10.1111\/j.1471-4159.2010.07033.x.","journal-title":"J Neurochem"},{"key":"1730_CR49","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1080\/15548627.2019.1628538","volume":"16","author":"C Sarkar","year":"2020","unstructured":"Sarkar C, et al. PLA2G4A\/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma. Autophagy. 2020;16:466\u201385. https:\/\/doi.org\/10.1080\/15548627.2019.1628538.","journal-title":"Autophagy"},{"key":"1730_CR50","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1242\/jcs.060681","volume":"123","author":"A Linetti","year":"2010","unstructured":"Linetti A, et al. Cholesterol reduction impairs exocytosis of synaptic vesicles. J Cell Sci. 2010;123:595\u2013605. https:\/\/doi.org\/10.1242\/jcs.060681.","journal-title":"J Cell Sci"},{"key":"1730_CR51","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1242\/jcs.205484","volume":"130","author":"E West","year":"2017","unstructured":"West E, Osborne C, Bate C. The cholesterol ester cycle regulates signalling complexes and synapse damage caused by amyloid-beta. J Cell Sci. 2017;130:3050\u20139. https:\/\/doi.org\/10.1242\/jcs.205484.","journal-title":"J Cell Sci"},{"key":"1730_CR52","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1038\/nn.2213","volume":"11","author":"RO Sanchez-Mejia","year":"2008","unstructured":"Sanchez-Mejia RO, et al. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer\u2019s disease. Nat Neurosci. 2008;11:1311\u20138. https:\/\/doi.org\/10.1038\/nn.2213.","journal-title":"Nat Neurosci"},{"key":"1730_CR53","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/hmg\/ddm029","volume":"16","author":"Z Zhang","year":"2007","unstructured":"Zhang Z, et al. Production of lysophosphatidylcholine by cPLA2 in the brain of mice lacking PPT1 is a signal for phagocyte infiltration. Hum Mol Genet. 2007;16:837\u201347. https:\/\/doi.org\/10.1093\/hmg\/ddm029.","journal-title":"Hum Mol Genet"},{"key":"1730_CR54","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s12192-020-01153-6","volume":"25","author":"A D'Anneo","year":"2020","unstructured":"D\u2019Anneo A, et al. Lipid chaperones and associated diseases: a group of chaperonopathies defining a new nosological entity with implications for medical research and practice. Cell Stress Chaperones. 2020;25:805\u201320. https:\/\/doi.org\/10.1007\/s12192-020-01153-6.","journal-title":"Cell Stress Chaperones"},{"key":"1730_CR55","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.neures.2014.08.012","volume":"102","author":"M Matsumata","year":"2016","unstructured":"Matsumata M, Inada H, Osumi N. Fatty acid binding proteins and the nervous system: their impact on mental conditions. Neurosci Res. 2016;102:47\u201355. https:\/\/doi.org\/10.1016\/j.neures.2014.08.012.","journal-title":"Neurosci Res"},{"key":"1730_CR56","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.brainres.2018.11.036","volume":"1707","author":"A Cheng","year":"2019","unstructured":"Cheng A, Shinoda Y, Yamamoto T, Miyachi H, Fukunaga K. Development of FABP3 ligands that inhibit arachidonic acid-induced alpha-synuclein oligomerization. Brain Res. 2019;1707:190\u20137. https:\/\/doi.org\/10.1016\/j.brainres.2018.11.036.","journal-title":"Brain Res"},{"key":"1730_CR57","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1620\/tjem.214.213","volume":"214","author":"Y Owada","year":"2008","unstructured":"Owada Y. Fatty acid binding protein: localization and functional significance in the brain. Tohoku J Exp Med. 2008;214:213\u201320. https:\/\/doi.org\/10.1620\/tjem.214.213.","journal-title":"Tohoku J Exp Med"},{"key":"1730_CR58","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1750-1326-8-39","volume":"8","author":"RS Desikan","year":"2013","unstructured":"Desikan RS, et al. Heart fatty acid binding protein and Abeta-associated Alzheimer\u2019s neurodegeneration. Mol Neurodegener. 2013;8:39. https:\/\/doi.org\/10.1186\/1750-1326-8-39.","journal-title":"Mol Neurodegener"},{"key":"1730_CR59","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13195-017-0276-4","volume":"9","author":"D Chiasserini","year":"2017","unstructured":"Chiasserini D, et al. Differential role of CSF fatty acid binding protein 3, alpha-synuclein, and Alzheimer\u2019s disease core biomarkers in Lewy body disorders and Alzheimer\u2019s dementia. Alzheimers Res Ther. 2017;9:52. https:\/\/doi.org\/10.1186\/s13195-017-0276-4.","journal-title":"Alzheimers Res Ther"},{"key":"1730_CR60","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/brain\/awaa376","volume":"144","author":"Z Ruan","year":"2021","unstructured":"Ruan Z, et al. Alzheimer\u2019s disease brain-derived extracellular vesicles spread tau pathology in interneurons. Brain. 2021;144:288\u2013309. https:\/\/doi.org\/10.1093\/brain\/awaa376.","journal-title":"Brain"},{"key":"1730_CR61","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.bbrc.2013.11.036","volume":"442","author":"A Ohkuni","year":"2013","unstructured":"Ohkuni A, Ohno Y, Kihara A. Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway. Biochem Biophys Res Commun. 2013;442:195\u2013201. https:\/\/doi.org\/10.1016\/j.bbrc.2013.11.036.","journal-title":"Biochem Biophys Res Commun"},{"key":"1730_CR62","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3389\/fncel.2013.00144","volume":"7","author":"G Hussain","year":"2013","unstructured":"Hussain G, Schmitt F, Loeffler JP, Gonzalez de Aguilar JL. Fatting the brain: a brief of recent research. Front Cell Neurosci. 2013;7:144. https:\/\/doi.org\/10.3389\/fncel.2013.00144.","journal-title":"Front Cell Neurosci"},{"key":"1730_CR63","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3233\/JAD-170974","volume":"62","author":"XY He","year":"2018","unstructured":"He XY, Isaacs C, Yang SY. Roles of mitochondrial 17beta-hydroxysteroid dehydrogenase type 10 in Alzheimer\u2019s disease. J Alzheimers Dis. 2018;62:665\u201373. https:\/\/doi.org\/10.3233\/JAD-170974.","journal-title":"J Alzheimers Dis"},{"key":"1730_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mce.2011.06.011","volume":"343","author":"SY Yang","year":"2011","unstructured":"Yang SY, He XY, Miller D. Hydroxysteroid (17beta) dehydrogenase X in human health and disease. Mol Cell Endocrinol. 2011;343:1\u20136. https:\/\/doi.org\/10.1016\/j.mce.2011.06.011.","journal-title":"Mol Cell Endocrinol"},{"key":"1730_CR65","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.brainres.2005.01.022","volume":"1040","author":"XY He","year":"2005","unstructured":"He XY, Wegiel J, Yang SY. Intracellular oxidation of allopregnanolone by human brain type 10 17beta-hydroxysteroid dehydrogenase. Brain Res. 2005;1040:29\u201335. https:\/\/doi.org\/10.1016\/j.brainres.2005.01.022.","journal-title":"Brain Res"},{"key":"1730_CR66","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41419-020-02763-9","volume":"11","author":"L Liu","year":"2020","unstructured":"Liu L, et al. Deacetylation of HSD17B10 by SIRT3 regulates cell growth and cell resistance under oxidative and starvation stresses. Cell Death Dis. 2020;11:563. https:\/\/doi.org\/10.1038\/s41419-020-02763-9.","journal-title":"Cell Death Dis"},{"key":"1730_CR67","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.jsbmb.2014.07.001","volume":"143","author":"SY Yang","year":"2014","unstructured":"Yang SY, et al. Roles of 17beta-hydroxysteroid dehydrogenase type 10 in neurodegenerative disorders. J Steroid Biochem Mol Biol. 2014;143:460\u201372. https:\/\/doi.org\/10.1016\/j.jsbmb.2014.07.001.","journal-title":"J Steroid Biochem Mol Biol"},{"key":"1730_CR68","doi-asserted-by":"publisher","unstructured":"Ingram-Smith C, Woods BI, Smith KS. Characterization of the acyl substrate binding pocket of acetyl-CoA synthetase. Biochemistry. 2006;45(38):11482\u201390. https:\/\/doi.org\/10.1021\/bi061023e.","DOI":"10.1021\/bi061023e"},{"key":"1730_CR69","doi-asserted-by":"publisher","unstructured":"MacInnes A, Fairman DA, Binding P, Rhodes J, Wyatt MJ, Phelan A, et al. The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2003;93(3):e26\u201332. https:\/\/doi.org\/10.1161\/01.RES.0000086943.72932.71.","DOI":"10.1161\/01.RES.0000086943.72932.71"},{"key":"1730_CR70","doi-asserted-by":"publisher","unstructured":"Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res. 2000;28(1):235\u201342. https:\/\/doi.org\/10.1093\/nar\/28.1.235.","DOI":"10.1093\/nar\/28.1.235"},{"key":"1730_CR71","doi-asserted-by":"publisher","unstructured":"Dezsi CA. Trimetazidine in practice: review of the clinical and experimental evidence. Am J Ther. 2016;23(3):e871\u20139. https:\/\/doi.org\/10.1097\/MJT.0000000000000180.","DOI":"10.1097\/MJT.0000000000000180"},{"key":"1730_CR72","doi-asserted-by":"publisher","unstructured":"Lee L, Wiggert B. Isolation and characterization of an unsaturated fatty acid-binding\nprotein from developing chick neural retina. J Neurochem. 1984;42(1):47\u201353. https:\/\/doi.org\/10.1111\/j.1471-4159.1984.tb09696.x.","DOI":"10.1111\/j.1471-4159.1984.tb09696.x"},{"key":"1730_CR73","doi-asserted-by":"publisher","unstructured":"Zanotti G, Scapin G, Spadon P, Veerkamp JH, Sacchettini JC. Three-dimensional structure of recombinant human muscle fatty acid-binding protein. J Biol Chem. 1992;267(26):18541\u201350. https:\/\/doi.org\/10.2210\/pdb2hmb\/pdb.","DOI":"10.2210\/pdb2hmb\/pdb"},{"key":"1730_CR74","doi-asserted-by":"crossref","unstructured":"Popov VN, Eprintsev AT, Fedorin DN, Fomenko O, Igamberdiev AU. Role of transamination in the mobilization of respiratory substrates in germinating seeds of castor oil plants. Prikl Biokhim Mikrobiol. 2007;43(3):376\u201381.","DOI":"10.1134\/S0003683807030179"},{"key":"1730_CR75","doi-asserted-by":"publisher","unstructured":"Ahn SJ, Yang CH, Cooksey DA. Pseudomonas putida 06909 genes expressed during colonization on mycelial surfaces and phenotypic characterization of mutants.J Appl Microbiol. 2007;103(1):120\u201332. https:\/\/doi.org\/10.1111\/j.1365-2672.2006.03232.x.","DOI":"10.1111\/j.1365-2672.2006.03232.x"},{"key":"1730_CR76","doi-asserted-by":"publisher","unstructured":"Johannessen CU, Johannessen SI. Valproate: past, present, and future. CNS Drug Rev. 2003;9(2):199\u2013216. https:\/\/doi.org\/10.1111\/j.1527-3458.2003.tb00249.x.","DOI":"10.1111\/j.1527-3458.2003.tb00249.x"},{"key":"1730_CR77","unstructured":"Kadow J, Wang HG, Lin PF. Small-molecule HIV-1 gp120 inhibitors to prevent HIV-1 entry: an emerging opportunity for drug development. Curr Opin Investig Drugs. 2006;7(8):721\u20136."}],"container-title":["European Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-024-01730-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40001-024-01730-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-024-01730-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T08:05:07Z","timestamp":1711353907000},"score":1,"resource":{"primary":{"URL":"https:\/\/eurjmedres.biomedcentral.com\/articles\/10.1186\/s40001-024-01730-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,25]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1730"],"URL":"https:\/\/doi.org\/10.1186\/s40001-024-01730-w","relation":{},"ISSN":["2047-783X"],"issn-type":[{"value":"2047-783X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,25]]},"assertion":[{"value":"10 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"199"}}