{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T21:05:37Z","timestamp":1776805537326,"version":"3.51.2"},"reference-count":90,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission under the framework programme of the European Union, LipiDiDiet","award":["211696"],"award-info":[{"award-number":["211696"]}]},{"name":"EU Joint Programme\u2014Neurodegenerative Disease Research (JPND) and BMBF grants MIND-AD","award":["01ED1509"],"award-info":[{"award-number":["01ED1509"]}]},{"name":"EURO-FINGERS","award":["01ED2003"],"award-info":[{"award-number":["01ED2003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by an increased plaque burden and tangle accumulation in the brain accompanied by extensive lipid alterations. Methylxanthines (MTXs) are alkaloids frequently consumed by dietary intake known to interfere with the molecular mechanisms leading to AD. Besides the fact that MTX consumption is associated with changes in triglycerides and cholesterol in serum and liver, little is known about the effect of MTXs on other lipid classes, which raises the question of whether MTX can alter lipids in a way that may be relevant in AD. Here we have analyzed naturally occurring MTXs caffeine, theobromine, theophylline, and the synthetic MTXs pentoxifylline and propentofylline also used as drugs in different neuroblastoma cell lines. Our results show that lipid alterations are not limited to triglycerides and cholesterol in the liver and serum, but also include changes in sphingomyelins, ceramides, phosphatidylcholine, and plasmalogens in neuroblastoma cells. These changes comprise alterations known to be beneficial, but also adverse effects regarding AD were observed. Our results give an additional perspective of the complex link between MTX and AD, and suggest combining MTX with a lipid-altering diet compensating the adverse effects of MTX rather than using MTX alone to prevent or treat AD.<\/jats:p>","DOI":"10.3390\/ijms23042295","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T09:18:42Z","timestamp":1645435122000},"page":"2295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Methylxanthines Induce a Change in the AD\/Neurodegeneration-Linked Lipid Profile in Neuroblastoma Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-0184","authenticated-orcid":false,"given":"Daniel","family":"Janitschke","sequence":"first","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-452X","authenticated-orcid":false,"given":"Anna Andrea","family":"Lauer","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornel Manuel","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakob","family":"Winkler","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-0188","authenticated-orcid":false,"given":"Lea Victoria","family":"Griebsch","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina Melanie","family":"Pilz","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Leoni","family":"Theiss","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike Sabine","family":"Grimm","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7481-6430","authenticated-orcid":false,"given":"Tobias","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"},{"name":"Deutsches Institut f\u00fcr Demenzpr\u00e4vention, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-6506","authenticated-orcid":false,"given":"Marcus Otto Walter","family":"Grimm","sequence":"additional","affiliation":[{"name":"Experimental Neurology, Saarland University, 66421 Homburg, Germany"},{"name":"Deutsches Institut f\u00fcr Demenzpr\u00e4vention, Saarland University, 66421 Homburg, Germany"},{"name":"Nutrition Therapy and Counseling, Campus Rheinland, SRH University of Applied Health Science, 51377 Leverkusen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","unstructured":"(2012). Livertox: Clinical and Research Information on Drug-Induced Liver Injury, National Institute of Diabetes and Digestive and Kidney Diseases."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arnaud, M.J. (2011). Pharmacokinetics and metabolism of natural methylxanthines in animal and man. Methylxanthines. Handbook of Experimental Pharmacology, Springer.","DOI":"10.1007\/978-3-642-13443-2_3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1007\/s11064-009-9945-4","article-title":"Interactions between chronic stress and chronic consumption of caffeine on the enzymatic antioxidant system","volume":"34","author":"Noschang","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s12640-012-9372-1","article-title":"Effects of adenosine receptor antagonists on the in vivo lps-induced inflammation model of parkinson\u2019s disease","volume":"24","author":"Golembiowska","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.2967\/jnumed.112.105114","article-title":"Caffeine occupancy of human cerebral a1 adenosine receptors: In vivo quantification with 18f-cpfpx and pet","volume":"53","author":"Elmenhorst","year":"2012","journal-title":"J. Nucl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1046\/j.1365-201x.2000.00742.x","article-title":"Distribution of adenosine a1, a2a and a2b receptors in human skeletal muscle","volume":"169","author":"Lynge","year":"2000","journal-title":"Acta Physiol. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0014-2999(82)90359-4","article-title":"Xanthine derivatives as adenosine receptor antagonists","volume":"81","author":"Fredholm","year":"1982","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0896-6273(91)90070-G","article-title":"The brain ryanodine receptor: A caffeine-sensitive calcium release channel","volume":"7","author":"McPherson","year":"1991","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0024-3205(88)90517-6","article-title":"Caffeine and theophylline analogues: Correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors","volume":"43","author":"Choi","year":"1988","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/0024-3205(79)90369-2","article-title":"Purinergic inhibition of diazepam binding to rat brain (in vitro)","volume":"24","author":"Marangos","year":"1979","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.pnpbp.2007.11.021","article-title":"A placebo controlled study of the propentofylline added to risperidone in chronic schizophrenia","volume":"32","author":"Salimi","year":"2008","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1600670","DOI":"10.1002\/mnfr.201600670","article-title":"Health benefits of methylxanthines in neurodegenerative diseases","volume":"61","author":"Franco","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Janitschke, D., Nelke, C., Lauer, A.A., Regner, L., Winkler, J., Thiel, A., Grimm, H.S., Hartmann, T., and Grimm, M.O.W. (2019). Effect of caffeine and other methylxanthines on abeta-homeostasis in sh-sy5y cells. Biomolecules, 9.","DOI":"10.3390\/biom9110689"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Janitschke, D., Lauer, A.A., Bachmann, C.M., Grimm, H.S., Hartmann, T., and Grimm, M.O.W. (2021). Methylxanthines and neurodegenerative diseases: An update. Nutrients, 13.","DOI":"10.3390\/nu13030803"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.3390\/nu5104159","article-title":"Health benefits of methylxanthines in cacao and chocolate","volume":"5","author":"Franco","year":"2013","journal-title":"Nutrients"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.rmed.2016.01.022","article-title":"The potential of methylxanthine-based therapies in pediatric respiratory tract diseases","volume":"112","author":"Franco","year":"2016","journal-title":"Respir. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3945\/ajcn.112.047373","article-title":"Effect of cocoa and theobromine consumption on serum hdl-cholesterol concentrations: A randomized controlled trial","volume":"97","author":"Neufingerl","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/chromsci\/45.5.273","article-title":"Determination of theobromine, theophylline, and caffeine in by-products of cupuacu and cacao seeds by high-performance liquid chromatography","volume":"45","author":"Lanuzza","year":"2007","journal-title":"J. Chromatogr. Sci."},{"key":"ref_19","first-page":"BR325-30","article-title":"Antioxidant and prooxidant properties of caffeine, theobromine and xanthine","volume":"9","author":"Azam","year":"2003","journal-title":"Med. Sci. Monit."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1523\/JNEUROSCI.19-10-04011.1999","article-title":"The stimulatory action and the development of tolerance to caffeine is associated with alterations in gene expression in specific brain regions","volume":"19","author":"Svenningsson","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s002280050205","article-title":"Absorption rate of methylxanthines following capsules, cola and chocolate","volume":"51","author":"Mumford","year":"1996","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0014-2999(99)00533-6","article-title":"Autoradiographic comparison of the potency of several structurally unrelated adenosine receptor antagonists at adenosine a1 and a(2a) receptors","volume":"380","author":"Fredholm","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1164\/rccm.200210-1142PP","article-title":"Theophylline: New perspectives for an old drug","volume":"167","author":"Barnes","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_24","first-page":"7S","article-title":"Theophylline as a bronchodilator in copd and its combination with inhaled beta-adrenergic drugs","volume":"92","author":"Jenne","year":"1987","journal-title":"Chest"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0190-9622(94)70069-9","article-title":"Pentoxifylline","volume":"30","author":"Samlaska","year":"1994","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/icb.1975.29","article-title":"The effects of a new xanthine derivative, 3,7-dimethyl-1(5-oxohexyl)-xanthin (pentoxifylline) on the general and cardiac haemodynamics of the intact animal","volume":"53","author":"Maxwell","year":"1975","journal-title":"Aust. J. Exp. Biol. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sweitzer, S., and De Leo, J. (2011). Propentofylline: Glial modulation, neuroprotection, and alleviation of chronic pain. Methylxanthines. Handbook of Experimental Pharmacology, Springer.","DOI":"10.1007\/978-3-642-13443-2_8"},{"key":"ref_28","first-page":"1210","article-title":"Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain","volume":"297","author":"Sweitzer","year":"2001","journal-title":"J. Pharmacol. Exp."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Janitschke, D., Lauer, A.A., Bachmann, C.M., Seyfried, M., Grimm, H.S., Hartmann, T., and Grimm, M.O.W. (2020). Unique role of caffeine compared to other methylxanthines (theobromine, theophylline, pentoxifylline, propentofylline) in regulation of ad relevant genes in neuroblastoma sh-sy5y wild type cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239015"},{"key":"ref_30","first-page":"395","article-title":"Effects of methylxanthines on lipid synthesis in developing neural systems","volume":"5","author":"Volpe","year":"1981","journal-title":"Semin. Perinatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1271\/bbb.70.1134","article-title":"Regulation of the body fat percentage in developmental-stage rats by methylxanthine derivatives in a high-fat diet","volume":"70","author":"Inoue","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Xicoy, H., Wieringa, B., and Martens, G.J.M. (2019). The role of lipids in parkinson\u2019s disease. Cells, 8.","DOI":"10.3390\/cells8010027"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3389\/fnmol.2017.00063","article-title":"App function and lipids: A bidirectional link","volume":"10","author":"Grimm","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"814390","DOI":"10.1155\/2013\/814390","article-title":"The impact of cholesterol, dha, and sphingolipids on Alzheimer\u2019s disease","volume":"2013","author":"Grimm","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.nbd.2007.10.005","article-title":"Cholesterol retention in Alzheimer\u2019s brain is responsible for high beta- and gamma-secretase activities and abeta production","volume":"29","author":"Xiong","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14028","DOI":"10.1074\/jbc.M110.182329","article-title":"Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms","volume":"286","author":"Grimm","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/sj.mp.4001509","article-title":"Gm1 ganglioside regulates the proteolysis of amyloid precursor protein","volume":"9","author":"Zha","year":"2004","journal-title":"Mol. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"141240","DOI":"10.1100\/2012\/141240","article-title":"Plasmalogens inhibit app processing by directly affecting gamma-secretase activity in Alzheimer\u2019s disease","volume":"2012","author":"Rothhaar","year":"2012","journal-title":"Sci. World J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1139\/bcb-2015-0149","article-title":"Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-beta by affecting insulin-degrading enzyme","volume":"94","author":"Grimm","year":"2016","journal-title":"Biochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mett, J., Lauer, A.A., Janitschke, D., Griebsch, L.V., Theiss, E.L., Grimm, H.S., Koivisto, H., Tanila, H., Hartmann, T., and Grimm, M.O.W. (2021). Medium-chain length fatty acids enhance a\u03b2 degradation by affecting insulin-degrading enzyme. Cells, 10.","DOI":"10.3390\/cells10112941"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.bbrc.2012.08.020","article-title":"Alzheimer\u2019s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. 1984","volume":"425","author":"Glenner","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2000632","DOI":"10.1002\/mnfr.202000632","article-title":"The effects of resveratrol, caffeine, beta-carotene, and epigallocatechin gallate (egcg) on amyloid- beta 25\u201335 aggregation in synthetic brain membranes","volume":"64","author":"Gastaldo","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Saiz-Vazquez, O., Puente-Martinez, A., Ubillos-Landa, S., Pacheco-Bonrostro, J., and Santabarbara, J. (2020). Cholesterol and Alzheimer\u2019s disease risk: A meta-meta-analysis. Brain Sci., 10.","DOI":"10.3390\/brainsci10060386"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fnagi.2020.00005","article-title":"Low-density lipoprotein cholesterol and Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"12","author":"Zhou","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/BF02536067","article-title":"Fatty acid composition of brain phospholipids in aging and in Alzheimer\u2019s disease","volume":"26","author":"Soderberg","year":"1991","journal-title":"Lipids"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1079\/BJN2002804","article-title":"Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer\u2019s disease: A case-control study","volume":"89","author":"Tully","year":"2003","journal-title":"Br. J. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1001\/archneur.60.7.940","article-title":"Consumption of fish and n-3 fatty acids and risk of incident alzheimer disease","volume":"60","author":"Morris","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1136\/bmj.325.7370.932","article-title":"Fish, meat, and risk of dementia: Cohort study","volume":"325","author":"Letenneur","year":"2002","journal-title":"BMJ"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3945\/an.111.000893","article-title":"Omega-3 fatty acids epa and dha: Health benefits throughout life","volume":"3","author":"Swanson","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12944-019-1044-1","article-title":"Plasmalogens and Alzheimer\u2019s disease: A review","volume":"18","author":"Su","year":"2019","journal-title":"Lipids Health Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1046\/j.1471-4159.2001.00332.x","article-title":"Plasmalogen deficiency in early Alzheimer\u2019s disease subjects and in animal models: Molecular characterization using electrospray ionization mass spectrometry","volume":"77","author":"Han","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0006-8993(95)00931-F","article-title":"Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer\u2019s disease brain","volume":"698","author":"Ginsberg","year":"1995","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1023\/A:1011603916962","article-title":"Brain membrane phospholipid alterations in Alzheimer\u2019s disease","volume":"26","author":"Pettegrew","year":"2001","journal-title":"Neurochem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1749-6632.2012.06641.x","article-title":"Effects of plasmalogens on systemic lipopolysaccharide-induced glial activation and beta-amyloid accumulation in adult mice","volume":"1262","author":"Katafuchi","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ebiom.2017.02.012","article-title":"Efficacy and blood plasmalogen changes by oral administration of plasmalogen in patients with mild Alzheimer\u2019s disease and mild cognitive impairment: A multicenter, randomized, double-blind, placebo-controlled trial","volume":"17","author":"Fujino","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Ifuku, M., Take, S., Kawamura, J., Miake, K., and Katafuchi, T. (2013). Plasmalogens rescue neuronal cell death through an activation of akt and erk survival signaling. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083508"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.bbalip.2010.05.013","article-title":"Phospholipase a2 and arachidonic acid in Alzheimer\u2019s disease","volume":"1801","author":"Mucke","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/nn.2213","article-title":"Phospholipase a2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer\u2019s disease","volume":"11","author":"Newman","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1503\/jpn.090059","article-title":"Circulating plasmalogen levels and alzheimer disease assessment scale-cognitive scores in alzheimer patients","volume":"35","author":"Wood","year":"2010","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1097\/NEN.0000000000000116","article-title":"Lysophosphatidylcholine and amide as metabolites for detecting alzheimer disease using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabonomics","volume":"73","author":"Cui","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s00702-003-0007-9","article-title":"Decreased lysophosphatidylcholine\/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer\u2019s disease","volume":"110","author":"Mulder","year":"2003","journal-title":"J. Neural Transm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2174\/1871524915666141216161246","article-title":"Plasma metabolic profiling of mild cognitive impairment and Alzheimer\u2019s disease using liquid chromatography\/mass spectrometry","volume":"14","author":"Liu","year":"2014","journal-title":"Cent. Nerv. Syst. Agents Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ncb1313","article-title":"Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin","volume":"7","author":"Grimm","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.neurobiolaging.2008.05.010","article-title":"Deregulation of sphingolipid metabolism in Alzheimer\u2019s disease","volume":"31","author":"He","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8653","DOI":"10.1523\/JNEUROSCI.1429-16.2016","article-title":"Neutral sphingomyelinase-2 deficiency ameliorates Alzheimer\u2019s disease pathology and improves cognition in the 5xfad mouse","volume":"36","author":"Dinkins","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1007\/s00702-005-0374-5","article-title":"High activity of acid sphingomyelinase in major depression","volume":"112","author":"Kornhuber","year":"2005","journal-title":"J. Neural. Transm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1046\/j.1471-4159.1996.66010362.x","article-title":"Characterization and expression of the human a2a adenosine receptor gene","volume":"66","author":"Peterfreund","year":"1996","journal-title":"J. Neurochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1038\/npp.2014.150","article-title":"Association of adenosine receptor gene polymorphisms and in vivo adenosine a1 receptor binding in the human brain","volume":"39","author":"Hohoff","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Nagpure, B.V., and Bian, J.S. (2014). Hydrogen sulfide inhibits a2a adenosine receptor agonist induced beta-amyloid production in sh-sy5y neuroblastoma cells via a camp dependent pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088508"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-2999(97)01194-1","article-title":"Protein kinase c regulates adenosine a2a receptor mrna expression in sh-sy5y cells","volume":"336","author":"Peterfreund","year":"1997","journal-title":"Eur. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.3390\/nu6041701","article-title":"A nutrient combination that can affect synapse formation","volume":"6","author":"Wurtman","year":"2014","journal-title":"Nutrients"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"440","DOI":"10.3389\/fnins.2017.00440","article-title":"High content analysis of hippocampal neuron-astrocyte co-cultures shows a positive effect of fortasyn connect on neuronal survival and postsynaptic maturation","volume":"11","author":"Broersen","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"869","DOI":"10.2174\/1567205015666180427142350","article-title":"Dietary fat intake and risk of Alzheimer\u2019s disease and dementia: A meta-analysis of cohort studies","volume":"15","author":"Ruan","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1016\/j.neurobiolaging.2014.02.030","article-title":"Saturated and trans fats and dementia: A systematic review","volume":"35","author":"Barnard","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1002\/alz.12154","article-title":"Dietary fatty acids and risk of Alzheimer\u2019s disease and related dementias: Observations from the washington heights-hamilton heights-inwood columbia aging project (whicap)","volume":"16","author":"Gustafson","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.plefa.2007.10.006","article-title":"Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer\u2019s disease\u2014But how and why?","volume":"78","author":"Das","year":"2008","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1254\/jphs.10R33FM","article-title":"Neuroprotective and ameliorative actions of polyunsaturated fatty acids against neuronal diseases: Beneficial effect of docosahexaenoic acid on cognitive decline in Alzheimer\u2019s disease","volume":"116","author":"Hashimoto","year":"2011","journal-title":"J. Pharmacol. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","article-title":"Measurement of protein using bicinchoninic acid","volume":"150","author":"Smith","year":"1985","journal-title":"Anal. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"15301","DOI":"10.1038\/s41598-021-94706-3","article-title":"Shotgun lipidomics of liver and brain tissue of Alzheimer\u2019s disease model mice treated with acitretin","volume":"11","author":"Lauer","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S0022-2275(20)33347-2","article-title":"Determination of cholesterol at the low picomole level by nano-electrospray ionization tandem mass spectrometry","volume":"40","author":"Sandhoff","year":"1999","journal-title":"J. Lipid Res."},{"key":"ref_81","doi-asserted-by":"crossref","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":"ref_82","doi-asserted-by":"crossref","unstructured":"Shui, G., Stebbins, J.W., Lam, B.D., Cheong, W.F., Lam, S.M., Gregoire, F., Kusonoki, J., and Wenk, M.R. (2011). Comparative plasma lipidome between human and cynomolgus monkey: Are plasma polar lipids good biomarkers for diabetic monkeys?. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019731"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11306-017-1312-x","article-title":"High-throughput extraction and quantification method for targeted metabolomics in murine tissues","volume":"14","author":"Zukunft","year":"2018","journal-title":"Metabolomics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1177\/1087057111402200","article-title":"Identification of a potential biomarker for fabp4 inhibition: The power of lipidomics in preclinical drug testing","volume":"16","author":"Suhre","year":"2011","journal-title":"J. Biomol. Screen"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10654-010-9524-7","article-title":"Questionnaire-based self-reported nutrition habits associate with serum metabolism as revealed by quantitative targeted metabolomics","volume":"26","author":"Altmaier","year":"2011","journal-title":"Eur. J. Epidemiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/ng.507","article-title":"A genome-wide perspective of genetic variation in human metabolism","volume":"42","author":"Illig","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/mnfr.200900116","article-title":"Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics","volume":"53","author":"Altmaier","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1093\/bioinformatics\/btn506","article-title":"A new rule-based algorithm for identifying metabolic markers in prostate cancer using tandem mass spectrometry","volume":"24","author":"Osl","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1002\/rcm.3591","article-title":"Isotope correction of mass spectrometry profiles","volume":"22","author":"Eibl","year":"2008","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6543","DOI":"10.1007\/s00216-015-8822-z","article-title":"Development of a mass-spectrometry-based lipidomics platform for the profiling of phospholipids and sphingolipids in brain tissues","volume":"407","author":"Zhang","year":"2015","journal-title":"Anal. Bioanal. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2295\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:22:47Z","timestamp":1760134967000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":90,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23042295"],"URL":"https:\/\/doi.org\/10.3390\/ijms23042295","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]}}}