{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:26:47Z","timestamp":1791559607805,"version":"4.3.4"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"18","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["745668"],"award-info":[{"award-number":["745668"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["AGL2017-89417-R"],"award-info":[{"award-number":["AGL2017-89417-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto de Investigaci\u00f3n en Ciencias de Alimentaci\u00f3n"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Anal Bioanal Chem"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:p>Alzheimer\u2019s disease (AD) is the most common form of dementia caused by a progressive loss of neurons from different regions of the brain. This multifactorial pathophysiology has been widely characterized by neuroinflammation, extensive oxidative damage, synaptic loss, and neuronal cell death. In this sense, the design of multi-target strategies to prevent or delay its progression is a challenging goal. In the present work, different in vitro assays including antioxidant, anti-inflammatory, and anti-cholinergic activities of a carotenoid-enriched extract from <jats:italic>Dunaliella salina<\/jats:italic> microalgae obtained by supercritical fluid extraction are studied. Moreover, its potential neuroprotective effect in the human neuron-like SH-SY5Y cell model against remarkable hallmarks of AD was also evaluated. In parallel, a comprehensive metabolomics study based on the use of charged-surface hybrid chromatography (CSH) and hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution tandem mass spectrometry (Q-TOF MS\/MS) was applied to evaluate the effects of the extract on the metabolism of the treated cells. The use of advanced bioinformatics and statistical tools allowed the identification of more than 314 metabolites in SH-SY5Y cells, of which a great number of phosphatidylcholines, triacylglycerols, and fatty acids were significantly increased, while several phosphatidylglycerols were decreased, compared to controls. These lipidomic changes in cells along with the possible role exerted by carotenoids and other minor compounds on the cell membrane might explain the observed neuroprotective effect of the <jats:italic>D. salina<\/jats:italic> extract. However, future experiments using in vivo models to corroborate this hypothesis must be carried out.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00216-021-03819-1","type":"journal-article","created":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T21:02:36Z","timestamp":1639861356000},"page":"5357-5371","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Study of the potential neuroprotective effect of Dunaliella salina extract in SH-SY5Y cell model"],"prefix":"10.1007","volume":"414","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4054-9666","authenticated-orcid":false,"given":"Roc\u00edo","family":"Gallego","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-5816","authenticated-orcid":false,"given":"Alberto","family":"Vald\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3134-5960","authenticated-orcid":false,"given":"Jos\u00e9 David","family":"S\u00e1nchez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2901-0053","authenticated-orcid":false,"given":"Zully J.","family":"Su\u00e1rez-Montenegro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2127-8303","authenticated-orcid":false,"given":"Elena","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-0217","authenticated-orcid":false,"given":"Alejandro","family":"Cifuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7214-6653","authenticated-orcid":false,"given":"Miguel","family":"Herrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"3819_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13195-017-0297-z","volume":"9","author":"M Crous-Bou","year":"2017","unstructured":"Crous-Bou M, Minguill\u00f3n C, Gramunt N, Molinuevo JL. Alzheimer\u2019s disease prevention: from risk factors to early intervention. Alzheimers Res Ther. 2017;9:71. https:\/\/doi.org\/10.1186\/s13195-017-0297-z.","journal-title":"Alzheimers Res Ther"},{"key":"3819_CR2","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.ijbiomac.2020.11.192","volume":"167","author":"H Ashrafian","year":"2021","unstructured":"Ashrafian H, Zadeh EH, Khan RH. Review on Alzheimer\u2019s disease: inhibition of amyloid beta and tau tangle formation. Int J Biol Macromol. 2021;167:382\u201394. https:\/\/doi.org\/10.1016\/j.ijbiomac.2020.11.192.","journal-title":"Int J Biol Macromol"},{"key":"3819_CR3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3389\/fncel.2015.00091","volume":"9","author":"AA Kritis","year":"2015","unstructured":"Kritis AA, Stamoula EG, Paniskaki KA, Vavilis TD. Researching glutamate \u2013 induced cytotoxicity in different cell lines: a comparative\/collective analysis\/study. Front Cell Neurosci. 2015;9:91. https:\/\/doi.org\/10.3389\/fncel.2015.00091.","journal-title":"Front Cell Neurosci"},{"key":"3819_CR4","doi-asserted-by":"publisher","first-page":"510","DOI":"10.2174\/156720511796391836","volume":"8","author":"Y Gu","year":"2011","unstructured":"Gu Y, Scarmeas N. Dietary patterns in Alzheimers disease and cognitive aging. Curr Alzheimer Res. 2011;8:510\u20139. https:\/\/doi.org\/10.2174\/156720511796391836.","journal-title":"Curr Alzheimer Res"},{"issue":"9","key":"3819_CR5","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.jalz.2015.04.011","volume":"11","author":"MC Morris","year":"2015","unstructured":"Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL, Bennett DA, et al. MIND diet slows cognitive decline with aging. Alzheimers Dement. 2015;11(9):1015\u201322. https:\/\/doi.org\/10.1016\/j.jalz.2015.04.011.","journal-title":"Alzheimers Dement"},{"issue":"3","key":"3819_CR6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3390\/antiox9030229","volume":"9","author":"W Grodzicki","year":"2020","unstructured":"Grodzicki W, Dziendzikowska K. The role of selected bioactive compounds in the prevention of Alzheimer\u2019s disease. Antioxidants. 2020;9(3):229. https:\/\/doi.org\/10.3390\/antiox9030229.","journal-title":"Antioxidants"},{"issue":"3","key":"3819_CR7","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.trci.2017.06.006","volume":"3","author":"K Mullan","year":"2017","unstructured":"Mullan K, Williams MA, Cardwell CR, McGuinness B, Passmore P, Silvestri G, et al. Serum concentrations of vitamin E and carotenoids are altered in Alzheimer\u2019s disease: a case-control study. Alzheimers Dement Transl Res Clin Interv. 2017;3(3):432\u20139. https:\/\/doi.org\/10.1016\/j.trci.2017.06.006.","journal-title":"Alzheimers Dement Transl Res Clin Interv"},{"key":"3819_CR8","doi-asserted-by":"publisher","first-page":"11413","DOI":"10.1021\/acssuschemeng.0c03991","volume":"8","author":"M Bueno","year":"2020","unstructured":"Bueno M, Vitali C, S\u00e1nchez-Mart\u00ednez JD, Mendiola JA, Cifuentes A, Ib\u00e1\u00f1ez E, et al. Compressed CO2 technologies for the recovery of carotenoid-enriched extracts from Dunaliella salina with Potential Neuroprotective Activity. ACS Sustain Chem Eng. 2020;8:11413\u201323. https:\/\/doi.org\/10.1021\/acssuschemeng.0c03991.","journal-title":"ACS Sustain Chem Eng"},{"key":"3819_CR9","doi-asserted-by":"publisher","first-page":"7355","DOI":"10.1007\/S12035-019-1605-3","volume":"56","author":"LM de Medeiros","year":"2019","unstructured":"de Medeiros LM, De Bastiani MA, Rico EP, Schonhofen P, Pfaffenseller B, Wollenhaupt-Aguiar B, et al. Cholinergic differentiation of human neuroblastoma SH-SY5Y cell line and its potential use as an in vitro model for Alzheimer\u2019s disease studies. Mol Neurobiol. 2019;56:7355\u201367. https:\/\/doi.org\/10.1007\/S12035-019-1605-3.","journal-title":"Mol Neurobiol"},{"issue":"25","key":"3819_CR10","doi-asserted-by":"publisher","first-page":"21596","DOI":"10.1021\/acsomega.9b03463","volume":"4","author":"M Jakubec","year":"2019","unstructured":"Jakubec M, Bari\u00e5s E, Kryuchkov F, Hj\u00f8rnevik LV, Halskau \u00d8. Fast and quantitative phospholipidomic analysis of SH-SY5Y neuroblastoma cell cultures using liquid chromatography\u2013tandem mass spectrometry and 31p nuclear magnetic resonance. ACS Omega. 2019;4(25):21596\u2013603. https:\/\/doi.org\/10.1021\/acsomega.9b03463.","journal-title":"ACS Omega"},{"issue":"8","key":"3819_CR11","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.3390\/biomedicines9081062","volume":"9","author":"I Kurokin","year":"2021","unstructured":"Kurokin I, Lauer AA, Janitschke D, Winkler J, Theiss EL, Griebsch LV, et al. Targeted lipidomics of mitochondria in a cellular Alzheimer\u2019s disease model. Biomed. 2021;9(8):1062. https:\/\/doi.org\/10.3390\/biomedicines9081062.","journal-title":"Biomed"},{"key":"3819_CR12","doi-asserted-by":"publisher","unstructured":"Gallego R, Su\u00e1rez-Montenegro ZJ, Ib\u00e1\u00f1ez E, Herrero M, Vald\u00e9s A, Cifuentes A. In vitro neuroprotective potential and lipidomics study of olive leaves extracts enriched in triterpenoids. Front Nutr. 2021;8:769218.\u00a0https:\/\/doi.org\/10.3389\/fnut.2021.769218.","DOI":"10.3389\/fnut.2021.769218"},{"issue":"7","key":"3819_CR13","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.3390\/foods10071507","volume":"10","author":"ZJ Su\u00e1rez-Montenegro","year":"2021","unstructured":"Su\u00e1rez-Montenegro ZJ, \u00c1lvarez-Rivera G, S\u00e1nchez-Mart\u00ednez JD, Gallego R, Vald\u00e9s A, Bueno M, et al. Neuroprotective effect of terpenoids recovered from olive oil by-products. Foods. 2021;10(7):1507. https:\/\/doi.org\/10.3390\/foods10071507.","journal-title":"Foods"},{"key":"3819_CR14","doi-asserted-by":"publisher","unstructured":"Nampoothiri M, Reddy ND, John J, Kumar N, Kutty Nampurath G, Rao Chamallamudi M. Insulin blocks glutamate-induced neurotoxicity in differentiated SH-SY5Y neuronal cells. Behav Neurol. 2014;2014:674164.\u00a0https:\/\/doi.org\/10.1155\/2014\/674164.","DOI":"10.1155\/2014\/674164"},{"key":"3819_CR15","doi-asserted-by":"publisher","first-page":"5058","DOI":"10.1038\/s41598-021-84590-2","volume":"11","author":"A Vald\u00e9s","year":"2021","unstructured":"Vald\u00e9s A, Lucio-Caza\u00f1a FJ, Castro-Puyana M, Garc\u00eda-Pastor C, Fiehn O, Marina ML. Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu. Sci Rep. 2021;11:5058. https:\/\/doi.org\/10.1038\/s41598-021-84590-2.","journal-title":"Sci Rep"},{"key":"3819_CR16","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nmeth.3393","volume":"12","author":"H Tsugawa","year":"2015","unstructured":"Tsugawa H, Cajka T, Kind T, Ma Y, Higgins B, Ikeda K, et al. MS-DIAL: data-independent MS\/MS deconvolution for comprehensive metabolome analysis. Nat Methods. 2015;12:523\u20136. https:\/\/doi.org\/10.1038\/nmeth.3393.","journal-title":"Nat Methods"},{"key":"3819_CR17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/S11306-007-0082-2","volume":"3","author":"LW Sumner","year":"2007","unstructured":"Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA, et al. Proposed minimum reporting standards for chemical analysis. Metabolomics. 2007;3:211\u201321. https:\/\/doi.org\/10.1007\/S11306-007-0082-2.","journal-title":"Metabolomics"},{"issue":"6","key":"3819_CR18","doi-asserted-by":"publisher","first-page":"3250","DOI":"10.1021\/acs.analchem.6b04372","volume":"89","author":"BC DeFelice","year":"2017","unstructured":"DeFelice BC, Mehta SS, Samra S, \u010cajka T, Wancewicz B, Fahrmann JF, et al. Mass spectral feature list optimizer (MS-FLO): A Tool To Minimize False Positive Peak reports in untargeted liquid chromatography\u2013mass spectroscopy (LC-MS) data processing. Anal Chem. 2017;89(6):3250\u20135. https:\/\/doi.org\/10.1021\/acs.analchem.6b04372.","journal-title":"Anal Chem"},{"issue":"1","key":"3819_CR19","doi-asserted-by":"publisher","first-page":"e86","DOI":"10.1002\/cpbi.86","volume":"68","author":"J Chong","year":"2019","unstructured":"Chong J, Wishart DS, Xia J. Using MetaboAnalyst 4.0 for Comprehensive and integrative metabolomics data analysis. Curr Protoc Bioinforma. 2019;68(1):e86. https:\/\/doi.org\/10.1002\/cpbi.86.","journal-title":"Curr Protoc Bioinforma"},{"key":"3819_CR20","doi-asserted-by":"publisher","first-page":"14567","DOI":"10.1038\/s41598-017-15231-w","volume":"7","author":"DK Barupal","year":"2017","unstructured":"Barupal DK, Fiehn O. Chemical similarity enrichment analysis (ChemRICH) as alternative to biochemical pathway mapping for metabolomic datasets. Sci Reports. 2017;7:14567. https:\/\/doi.org\/10.1038\/s41598-017-15231-w.","journal-title":"Sci Reports"},{"key":"3819_CR21","doi-asserted-by":"publisher","unstructured":"Dos Santos TC, Gomes TM, Pinto BAS, Camara AL, Paes AMA. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer\u2019s disease therapy. Front Pharmacol. 2018;9:1192. https:\/\/doi.org\/10.3389\/FPHAR.2018.01192.","DOI":"10.3389\/FPHAR.2018.01192"},{"key":"3819_CR22","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.ejmech.2018.07.033","volume":"156","author":"D Knez","year":"2018","unstructured":"Knez D, Coquelle N, Pi\u0161lar A, \u017dakelj S, Juki\u010d M, Sova M, et al. Multi-target-directed ligands for treating Alzheimer\u2019s disease: butyrylcholinesterase inhibitors displaying antioxidant and neuroprotective activities. Eur J Med Chem. 2018;156:598\u2013617. https:\/\/doi.org\/10.1016\/j.ejmech.2018.07.033.","journal-title":"Eur J Med Chem"},{"issue":"1","key":"3819_CR23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2174\/1570159x13666150716165726","volume":"14","author":"TH Ferreira-Vieira","year":"2016","unstructured":"Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer\u2019s disease: targeting the cholinergic system. Curr Neuropharmacol. 2016;14(1):101\u201315. https:\/\/doi.org\/10.2174\/1570159x13666150716165726.","journal-title":"Curr Neuropharmacol"},{"key":"3819_CR24","doi-asserted-by":"publisher","first-page":"153676","DOI":"10.1016\/j.phymed.2021.153676","volume":"91","author":"J Manochkumar","year":"2021","unstructured":"Manochkumar J, Doss CGP, El-Seedi HR, Efferth T, Ramamoorthy S. The neuroprotective potential of carotenoids in vitro and in vivo. Phytomedicine. 2021;91:153676. https:\/\/doi.org\/10.1016\/j.phymed.2021.153676.","journal-title":"Phytomedicine"},{"key":"3819_CR25","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.intimp.2018.05.022","volume":"61","author":"L Zhou","year":"2018","unstructured":"Zhou L, Ouyang L, Lin S, Chen S, Liu Y, Zhou W, et al. Protective role of \u03b2-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury. Int Immunopharmacol. 2018;61:92\u20139. https:\/\/doi.org\/10.1016\/j.intimp.2018.05.022.","journal-title":"Int Immunopharmacol"},{"key":"3819_CR26","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3389\/fnmol.2019.00020","volume":"12","author":"R Crupi","year":"2019","unstructured":"Crupi R, Impellizzeri D, Cuzzocrea S. Role of metabotropic glutamate receptors in neurological disorders. Front Mol Neurosci. 2019;12:20. https:\/\/doi.org\/10.3389\/fnmol.2019.00020.","journal-title":"Front Mol Neurosci"},{"key":"3819_CR27","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/S10565-016-9360-Y","volume":"33","author":"T Liu","year":"2016","unstructured":"Liu T, Liu W, Zhao J, Meng F, Wang H. Lutein protects against \u03b2-amyloid peptide-induced oxidative stress in cerebrovascular endothelial cells through modulation of Nrf-2 and NF-\u03bab. Cell Biol Toxicol. 2016;33:57\u201367. https:\/\/doi.org\/10.1007\/S10565-016-9360-Y.","journal-title":"Cell Biol Toxicol"},{"issue":"8","key":"3819_CR28","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3390\/nu9080883","volume":"9","author":"S Hwang","year":"2017","unstructured":"Hwang S, Lim JW, Kim H. Inhibitory effect of lycopene on amyloid-\u03b2-induced apoptosis in neuronal cells. Nutr. 2017;9(8):883. https:\/\/doi.org\/10.3390\/nu9080883.","journal-title":"Nutr"},{"issue":"20","key":"3819_CR29","doi-asserted-by":"publisher","first-page":"4092","DOI":"10.1021\/acs.jafc.7b00805","volume":"65","author":"S Xiang","year":"2017","unstructured":"Xiang S, Liu F, Lin J, Chen H, Huang C, Chen L, et al. Fucoxanthin inhibits \u03b2-amyloid assembly and attenuates \u03b2-amyloid oligomer-induced cognitive impairments. J Agric Food Chem. 2017;65(20):4092\u2013102. https:\/\/doi.org\/10.1021\/acs.jafc.7b00805.","journal-title":"J Agric Food Chem"},{"key":"3819_CR30","doi-asserted-by":"publisher","first-page":"113168","DOI":"10.1016\/j.ejmech.2021.113168","volume":"213","author":"G Gonzalez","year":"2021","unstructured":"Gonzalez G, Hodo\u0148 J, Kazakova A, D\u2019Acunto CW, Ka\u0148ovsk\u00fd P, Urban M, et al. Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models. Eur J Med Chem. 2021;213:113168. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113168.","journal-title":"Eur J Med Chem"},{"key":"3819_CR31","doi-asserted-by":"publisher","first-page":"174336","DOI":"10.1016\/j.ejphar.2021.174336","volume":"908","author":"FB Brasil","year":"2021","unstructured":"Brasil FB, de Almeida FJS, Luckachaki MD, Dall\u2019Oglio EL, de Oliveira MR. Astaxanthin prevents mitochondrial impairment in the dopaminergic SH-SY5Y cell line exposed to glutamate-mediated excitotoxicity: Role for the Nrf2\/HO-1\/CO-BR axis. Eur J Pharmacol. 2021;908:174336. https:\/\/doi.org\/10.1016\/j.ejphar.2021.174336.","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"3819_CR32","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.3390\/ijms21041505","volume":"21","author":"Y-C Kao","year":"2020","unstructured":"Kao Y-C, Ho P-C, Tu Y-K, Jou I-M, Tsai K-J. Lipids and Alzheimer\u2019s disease. Int J Mol Sci. 2020;21(4):1505. https:\/\/doi.org\/10.3390\/ijms21041505.","journal-title":"Int J Mol Sci"},{"key":"3819_CR33","doi-asserted-by":"publisher","first-page":"111264","DOI":"10.1016\/j.exger.2021.111264","volume":"147","author":"I Blasko","year":"2021","unstructured":"Blasko I, Defrancesco M, Oberacher H, Loacker L, Kemmler G, Marksteiner J, et al. Plasma phosphatidylcholines and vitamin B12\/folate levels are possible prognostic biomarkers for progression of Alzheimer\u2019s disease. Exp Gerontol. 2021;147:111264. https:\/\/doi.org\/10.1016\/j.exger.2021.111264.","journal-title":"Exp Gerontol"},{"issue":"3","key":"3819_CR34","doi-asserted-by":"publisher","first-page":"809","DOI":"10.3233\/jad-160645","volume":"60","author":"M Kim","year":"2016","unstructured":"Kim M, Nevado-Holgado A, Whiley L, Snowden SG, Soininen H, Kloszewska I, et al. Association between plasma ceramides and phosphatidylcholines and hippocampal brain volume in late onset Alzheimer\u2019s disease. J Alzheimers Dis. 2016;60(3):809\u201317. https:\/\/doi.org\/10.3233\/jad-160645.","journal-title":"J Alzheimers Dis"},{"key":"3819_CR35","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, Zhong X, Mhyre TR, MacArthur LH, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014;20:415\u20138. https:\/\/doi.org\/10.1038\/nm.3466.","journal-title":"Nat Med"},{"key":"3819_CR36","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.brainres.2016.04.035","volume":"1642","author":"M Ko","year":"2016","unstructured":"Ko M, Hattori T, Abdullah M, Gong JS, Yamane T, Michikawa M. Phosphatidylcholine protects neurons from toxic effects of amyloid \u03b2-protein in culture. Brain Res. 2016;1642:376\u201383. https:\/\/doi.org\/10.1016\/j.brainres.2016.04.035.","journal-title":"Brain Res"},{"key":"3819_CR37","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1039\/d0mo00186d","volume":"17","author":"SK Byeon","year":"2021","unstructured":"Byeon SK, Madugundu AK, Jain AP, Bhat FA, Jung JH, Renuse S, et al. Cerebrospinal fluid lipidomics for biomarkers of Alzheimer\u2019s disease. Mol Omi. 2021;17:454\u201363. https:\/\/doi.org\/10.1039\/d0mo00186d.","journal-title":"Mol Omi"},{"key":"3819_CR38","doi-asserted-by":"publisher","first-page":"14509","DOI":"10.1038\/s41598-020-71510-z","volume":"10","author":"X Zhang","year":"2020","unstructured":"Zhang X, Liu W, Zan J, Wu C. Tan W (2020) Untargeted lipidomics reveals progression of early Alzheimer\u2019s disease in APP\/PS1 transgenic mice. Sci Reports. 2020;10:14509. https:\/\/doi.org\/10.1038\/s41598-020-71510-z.","journal-title":"Sci Reports"},{"key":"3819_CR39","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/1476-511x-12-68","volume":"12","author":"Y Tajima","year":"2013","unstructured":"Tajima Y, Ishikawa M, Maekawa K, Murayama M, Senoo Y, Nishimaki-Mogami T, et al. Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein\/tau for Alzheimer\u2019s disease. Lipids Heal Dis. 2013;12:68. https:\/\/doi.org\/10.1186\/1476-511x-12-68.","journal-title":"Lipids Heal Dis"},{"key":"3819_CR40","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nrn3820","volume":"15","author":"RP Bazinet","year":"2014","unstructured":"Bazinet RP, Lay\u00e9 S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15:771\u201385. https:\/\/doi.org\/10.1038\/nrn3820.","journal-title":"Nat Rev Neurosci"},{"key":"3819_CR41","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.abb.2018.12.027","volume":"663","author":"AE Shatshat","year":"2019","unstructured":"Shatshat AE, Pham AT, Rao PPN. Interactions of polyunsaturated fatty acids with amyloid peptides A\u03b240 and A\u03b242. Arch Biochem Biophys. 2019;663:34\u201343. https:\/\/doi.org\/10.1016\/j.abb.2018.12.027.","journal-title":"Arch Biochem Biophys"},{"key":"3819_CR42","doi-asserted-by":"publisher","first-page":"5243453","DOI":"10.1155\/2020\/5243453","volume":"2020","author":"M Yi","year":"2020","unstructured":"Yi M, Zhang C, Zhang Z, Yi P, Xu P, Huang J, et al. (2020) Integrated metabolomic and lipidomic analysis reveals the neuroprotective mechanisms of bushen tiansui formula in an A\u03b21-42-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":"3819_CR43","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3389\/fneur.2018.00104","volume":"9","author":"WS Kim","year":"2018","unstructured":"Kim WS, Jary E, Pickford R, He Y, Ahmed RM, Piguet O, et al. Lipidomics Analysis of behavioral variant frontotemporal dementia: a scope for biomarker development. Front Neurol. 2018;9:104. https:\/\/doi.org\/10.3389\/fneur.2018.00104.","journal-title":"Front Neurol"},{"issue":"4","key":"3819_CR44","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.3233\/jad-141002","volume":"43","author":"VF Monteiro-Cardoso","year":"2015","unstructured":"Monteiro-Cardoso VF, Oliveira MM, Melo T, Domingues MRM, Moreira PI, Ferreiro E, et al. Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer\u2019s disease. J Alzheimers Dis. 2015;43(4):1375\u201392. https:\/\/doi.org\/10.3233\/jad-141002.","journal-title":"J Alzheimers Dis"},{"issue":"6","key":"3819_CR45","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1194\/jlr.m093161","volume":"60","author":"BO Durojaye","year":"2019","unstructured":"Durojaye BO, Riedl KM, Curley RW Jr, Harrison EH. Uptake and metabolism of \u03b2-apo-8\u2032-carotenal, \u03b2-apo-10\u2032-carotenal, and \u03b2-apo-13-carotenone in Caco-2 cells. J Lipid Res. 2019;60(6):1121\u201335. https:\/\/doi.org\/10.1194\/jlr.m093161.","journal-title":"J Lipid Res"},{"issue":"13","key":"3819_CR46","doi-asserted-by":"publisher","first-page":"4330","DOI":"10.1021\/jf040028k","volume":"52","author":"C-S Liu","year":"2004","unstructured":"Liu C-S, Glahn RP, Liu RH. Assessment of carotenoid bioavailability of whole foods using a Caco-2 cell culture model coupled with an in vitro digestion. J Agric Food Chem. 2004;52(13):4330\u20137. https:\/\/doi.org\/10.1021\/jf040028k.","journal-title":"J Agric Food Chem"},{"issue":"3","key":"3819_CR47","first-page":"156","volume":"8","author":"N Craft","year":"2004","unstructured":"Craft N, Haitema T, Garnett K, Fitch K, Dorey C. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging. 2004;8(3):156\u201362.","journal-title":"J Nutr Health Aging"},{"issue":"22","key":"3819_CR48","doi-asserted-by":"publisher","first-page":"5553","DOI":"10.3390\/ijms20225553","volume":"20","author":"J Lakey-Beitia","year":"2019","unstructured":"Lakey-Beitia J, Kumar J, Hegde ML, Rao KS. Carotenoids as novel therapeutic molecules against neurodegenerative disorders: chemistry and molecular docking analysis. Int J Mol Sci. 2019;20(22):5553. https:\/\/doi.org\/10.3390\/ijms20225553.","journal-title":"Int J Mol Sci"}],"container-title":["Analytical and Bioanalytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00216-021-03819-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00216-021-03819-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00216-021-03819-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T02:05:13Z","timestamp":1656554713000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00216-021-03819-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,18]]},"references-count":48,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["3819"],"URL":"https:\/\/doi.org\/10.1007\/s00216-021-03819-1","relation":{},"ISSN":["1618-2642","1618-2650"],"issn-type":[{"value":"1618-2642","type":"print"},{"value":"1618-2650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,18]]},"assertion":[{"value":"20 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2021","order":4,"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"}},{"value":"The authors declare competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}