{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:12:44Z","timestamp":1791655964687,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00570"],"award-info":[{"award-number":["PI19\/00570"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) and other dementias are becoming increasingly common in the older population, and the number of people affected is expected to increase in a few years. Nowadays, biomarkers used in early AD diagnosis are expensive and invasive. Therefore, this research field is growing. In fact, peroxidation by-products derived from the oxidation of brain lipids (arachidonic (AA), docosahexanoic (DHA) and adrenic acid (AdA)) could be potential biomarkers, participating in the mechanisms of inflammation, neurotoxicity and cell death in AD pathology. Previous studies have shown specificity between lipid peroxidation compounds and other dementias (e.g., Lewy bodies (DLB), frontotemporal dementia (FTD)), but more research is required. Lipid peroxidation compounds (prostaglandins, isoprostanes, isofurans, neuroprostanes, neurofurans, dihomo-isoprostanes and dihomo-isofurans) were analysed by liquid chromatography and mass spectrometry in plasma samples from participants classified into a healthy group (n = 80), a mild cognitive impairment due to AD group (n = 106), a mild dementia due to AD group (n = 70), an advanced dementia due to AD group (n = 11) and a group of other non-AD dementias (n = 20). Most of these compounds showed statistically significant differences between groups (p &lt; 0.05), showing higher levels for the healthy and non-AD groups than the AD groups. Then, a multivariate analysis was carried out on these compounds, showing good diagnosis indexes (AUC 0.77, sensitivity 81.3%, positive predictive value 81%). Moreover, evaluating AD disease prognosis, two compounds (15-F2t-IsoP and 14(RS)-14-F4t-NeuroP) and three total parameters (isoprostanes, isofurans and neurofurans) showed significant differences among groups. Some compounds derived from the oxidation of AA, DHA and AdA have demonstrated their potential use in differential AD diagnosis. Specifically, 15-F2t-IsoP, 14(RS)-14-F4t-NeuroP and the total parameters for isoprostanes, isofurans and neurofurans have shown prognostic value for AD from its earliest stages to its most severe form.<\/jats:p>","DOI":"10.3390\/antiox11030551","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T03:06:10Z","timestamp":1647313570000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Assessment of Lipid Peroxidation in Alzheimer\u2019s Disease Differential Diagnosis and Prognosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-4761","authenticated-orcid":false,"given":"Laura","family":"Ferr\u00e9-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease Research Group, Health Research Institute La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pe\u00f1a-Bautista","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Group, Health Research Institute La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Baquero","sequence":"additional","affiliation":[{"name":"Division of Neurology, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-5877","authenticated-orcid":false,"given":"Consuelo","family":"Ch\u00e1fer-Peric\u00e1s","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Group, Health Research Institute La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","first-page":"149","article-title":"Epidemiology of Alzheimer\u2019s disease: Latest trends","volume":"70","author":"Durmugier","year":"2020","journal-title":"Rev. Prat."},{"key":"ref_2","unstructured":"World Health Organization (2021, October 13). Global Action Plan on the Public Health Response to Dementia. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dementia."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.2174\/1567205016666190517121140","article-title":"Biomarkers for Alzheimer\u2019s Disease","volume":"16","author":"Maccioni","year":"2019","journal-title":"Curr. Alzheimer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.12688\/f1000research.14506.1","article-title":"Current understanding of Alzheimer\u2019s disease diagnosis and treatment","volume":"7","author":"Weller","year":"2018","journal-title":"F1000Research"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.freeradbiomed.2012.09.027","article-title":"Lipid peroxidation triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain","volume":"62","author":"Sultana","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"572491","DOI":"10.1155\/2014\/572491","article-title":"Isoprostanes and Neuroprostanes as Biomarkers of Oxidative Stress in Neurodegenerative Diseases","volume":"2014","author":"Miller","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0002-9440(10)63968-5","article-title":"Brain Regional Quantification of F-Ring and D-\/E-Ring Isoprostanes and Neuroprostanes in Alzheimer\u2019s Disease","volume":"158","author":"Reich","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sidorova, Y., and Domanskyi, A. (2020). Detecting Oxidative Stress Biomarkers in Neurodegenerative Disease Models and Patients. Methods Protoc., 3.","DOI":"10.3390\/mps3040066"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e21990","DOI":"10.1002\/syn.21990","article-title":"Alzheimer\u2019s disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration","volume":"71","author":"Espinosa","year":"2017","journal-title":"Synapse"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.brainresbull.2016.06.005","article-title":"Oxidative stress, protein modification and Alzheimer disease","volume":"133","author":"Tramutola","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1080\/10715762.2017.1315114","article-title":"In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer\u2019s disease, Parkinson\u2019s disease, and diabetes","volume":"51","author":"Umeno","year":"2017","journal-title":"Free Radic. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.bbrc.2016.10.086","article-title":"Lipid peroxidation in cell death","volume":"482","author":"Gaschler","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/med.21712","article-title":"Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention","volume":"41","author":"Angelova","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Bautista, C., \u00c1lvarez, L., Durand, T., Vigor, C., Cuevas, A., Baquero, M., Vento, M., Herv\u00e1s, D., and Ch\u00e1fer-Peric\u00e1s, C. (2020). Clinical Utility of Plasma Lipid Peroxidation Biomarkers in Alzheimer\u2019s Disease Differential Diagnosis. Antioxidants, 9.","DOI":"10.3390\/antiox9080649"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3164\/jcbn.14-10","article-title":"The role of lipid peroxidation in neurological disorders","volume":"54","author":"Shichiri","year":"2014","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.13075\/ijomeh.1896.00596","article-title":"Isoprostanes\u2014A novel major group of oxidative stress markers","volume":"29","author":"Czerska","year":"2015","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kao, Y.-C., Ho, P.-C., Tu, Y.-K., Jou, I.-M., and Tsai, K.-J. (2020). Lipids and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041505"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00204-015-1517-6","article-title":"Biomarkers of lipid peroxidation in Alzheimer disease (AD): An update","volume":"89","author":"Lovell","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1212\/01.WNL.0000070185.02546.5D","article-title":"Enhanced brain levels of 8,12-iso-iPF2 -VI differentiate AD from frontotemporal dementia","volume":"61","author":"Yao","year":"2003","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41582-020-0348-0","article-title":"An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders","volume":"16","author":"Ashton","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fneur.2018.00104","article-title":"Lipidomics Analysis of Behavioral Variant Frontotemporal Dementia: A Scope for Biomarker Development","volume":"9","author":"Kim","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1038\/s41598-020-60457-w","article-title":"Uncovering pathophysiological changes in frontotemporal dementia using serum lipids","volume":"10","author":"Phan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nasaruddin, M.L., Pan, X., McGuinness, B., Passmore, P., Kehoe, P.G., H\u00f6lscher, C., Graham, S.F., and Green, B.D. (2018). Evidence That Parietal Lobe Fatty Acids May Be More Profoundly Affected in Moderate Alzheimer\u2019s Disease (AD) Pathology Than in Severe AD Pathology. Metabolites, 8.","DOI":"10.3390\/metabo8040069"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1097\/00002093-199700112-00005","article-title":"An inventory to assess activities of daily living for clinical trials in Alzheimer\u2019s disease. The Alzheimer\u2019s Disease Cooperative Study","volume":"11","author":"Galasko","year":"1997","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1192\/bjp.140.6.566","article-title":"A New Clinical Scale for the Staging of Dementia","volume":"140","author":"Hughes","year":"1982","journal-title":"Br. J. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/geronj\/37.3.323","article-title":"Measurement of Functional Activities in Older Adults in the Community","volume":"37","author":"Pfeffer","year":"1982","journal-title":"J. Gerontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1076\/jcen.20.3.310.823","article-title":"The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): Preliminary Clinical Validity","volume":"20","author":"Randolph","year":"1998","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.bcp.2013.12.014","article-title":"Therapeutic implications of the prostaglandin pathway in Alzheimer\u2019s disease","volume":"88","author":"Cudaback","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0361-9230(01)00450-6","article-title":"Sign of lipid peroxidation as measured in the urine of patients with probable Alzheimer\u2019s disease","volume":"54","author":"Tuppo","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.talanta.2018.03.002","article-title":"Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers","volume":"184","author":"Oger","year":"2018","journal-title":"Talanta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1023\/A:1007608615682","article-title":"Isoprostanes, Novel Markers of Oxidative Injury, Help Understanding the Pathogenesis of Neurodegenerative Diseases","volume":"25","author":"Greco","year":"2000","journal-title":"Neurochem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1093\/jnen\/59.10.866","article-title":"Increased Brain Synthesis of Prostaglandin E 2 and F 2 -Isoprostane in Human and Experimental Transmissible Spongiform Encephalopathies","volume":"59","author":"Minghetti","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1002\/jnr.21268","article-title":"Interactions between neural membrane glycerophospholipid and sphingolipid mediators: A recipe for neural cell survival or suicide","volume":"85","author":"Farooqui","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2012.09.030","article-title":"Measurement of F2- isoprostanes and isofurans using gas chromatography\u2013mass spectrometry","volume":"59","author":"Milne","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S0002-9440(10)65185-1","article-title":"The Magnitude of Brain Lipid Peroxidation Correlates with the Extent of Degeneration but Not with Density of Neuritic Plaques or Neurofibrillary Tangles or with APOE Genotype in Alzheimer\u2019s Disease Patients","volume":"155","author":"Montine","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.chemphyslip.2003.10.010","article-title":"Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases","volume":"128","author":"Montine","year":"2004","journal-title":"Chem. Phys. Lipids"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Snowden, S.G., Ebshiana, A.A., Hye, A., An, Y., Pletnikova, O., O\u2019Brien, R., Troncoso, J., Legido-Quigley, C., and Thambisetty, M. (2017). Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002266"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1212\/WNL.61.4.436","article-title":"Brain isoprostanes: A marker of lipid peroxidation and oxidative stress in AD","volume":"61","author":"Irizarry","year":"2003","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/WNN.0b013e31817995e7","article-title":"F2 Isoprostane Levels in Plasma and Urine do not Support Increased Lipid Peroxidation in Cognitively Impaired Parkinson Disease Patients","volume":"21","author":"Connolly","year":"2008","journal-title":"Cogn. Behav. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1046\/j.1471-4159.2003.01709.x","article-title":"Isofurans, but not F2-isoprostanes, are increased in the substantia nigra of patients with Parkinson\u2019s disease and with dementia with Lewy body disease","volume":"85","author":"Fessel","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.prostaglandins.2013.04.003","article-title":"Isoprostanes and neuroprostanes: Total synthesis, biological activity and biomarkers of oxidative stress in humans","volume":"107","author":"Galano","year":"2013","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1042\/EBC20190096","article-title":"Moving forward with isoprostanes, neuroprostanes and phytoprostanes: Where are we now?","volume":"64","author":"Ahmed","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"816","DOI":"10.3109\/10715762.2014.960867","article-title":"Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples","volume":"49","author":"Leung","year":"2015","journal-title":"Free Radic. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ana.10272","article-title":"Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer\u2019s disease","volume":"52","author":"Montine","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"741","DOI":"10.3233\/JAD-2010-100405","article-title":"Role of By-Products of Lipid Oxidation in Alzheimer\u2019s Disease Brain: A Focus on Acrolein","volume":"21","author":"Singh","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1074\/jbc.M706124200","article-title":"Neurofurans, Novel Indices of Oxidant Stress Derived from Docosahexaenoic Acid","volume":"283","author":"Song","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S219","DOI":"10.1194\/jlr.R800037-JLR200","article-title":"Isoprostanes","volume":"50","author":"Roberts","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1194\/jlr.M700503-JLR200","article-title":"F2-Dihomo-isoprostanes arise from free radical attack on adrenic acid","volume":"49","author":"VanRollins","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.freeradbiomed.2014.11.005","article-title":"Dihomo-isoprostanes\u2014nonenzymatic metabolites of AdA\u2014are higher in epileptic patients compared to healthy individuals by a new ultrahigh pressure liquid chromatography\u2013triple quadrupole\u2013tandem mass spectrometry method","volume":"79","author":"Medina","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1194\/jlr.P017798","article-title":"F2-dihomo-isoprostanes as potential early biomarkers of lipid oxidative damage in Rett syndrome","volume":"52","author":"Signorini","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/brain\/116.3.717","article-title":"Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer\u2019s disease and control subjects","volume":"116","author":"Skinner","year":"1993","journal-title":"Brain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S1357-2725(97)00125-8","article-title":"Abnormal content of n\u22126 and n\u22123 long-chain unsaturated fatty acids in the phosphoglycerides and cholesterol esters of parahippocampal cortex from Alzheimer\u2019s disease patients and its relationship to acetyl CoA content","volume":"30","author":"Corrigan","year":"1998","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e494","DOI":"10.1038\/tp.2014.127","article-title":"Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer\u2019s disease","volume":"5","author":"Proitsi","year":"2015","journal-title":"Transl. Psychiatry"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/3\/551\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:36:22Z","timestamp":1760135782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/3\/551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["antiox11030551"],"URL":"https:\/\/doi.org\/10.3390\/antiox11030551","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]}}}