{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T01:25:42Z","timestamp":1784942742772,"version":"3.55.0"},"reference-count":126,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T00:00:00Z","timestamp":1679097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Alzheimer's disease (AD) is a debilitating neurodegenerative disorder, characterized by memory deficit and dementia. AD is considered a multifactorial disorder where multiple processes like amyloid\u2010beta and tau accumulation, axonal degeneration, synaptic plasticity, and autophagic processes plays an important role. In this study, the spatial proteomic differences in the neonatal 5xFAD brain tissue were investigated using MALDI\u2010MSI coupled to LC\u2010MS\/MS, and the statistically significantly altered proteins were associated with AD. Thirty\u2010five differentially expressed proteins (DEPs) between the brain tissues of neonatal 5xFAD and their littermate mice were detected via MALDI\u2010MSI technique. Among the 35 proteins identified, 26 of them were directly associated with AD. Our results indicated a remarkable resemblance in the protein expression profiles of neonatal 5xFAD brain when compared to AD patient specimens or AD mouse models. These findings showed that the molecular alterations in the AD brain existed even at birth and that some proteins are neurodegenerative presages in neonatal AD brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Spatial proteomic alterations in the 5xFAD mouse brain compared to the littermate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>26 out of 35 differentially expressed proteins associated with Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Molecular alterations and neurodegenerative presages in neonatal AD brain.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Alterations in the synaptic function an early and common neurobiological thread.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13008","type":"journal-article","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T01:24:06Z","timestamp":1679189046000},"page":"4572-4589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Detection of early proteomic alterations in 5xFAD Alzheimer's disease neonatal mouse model via MALDI\u2010MSI"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-0023","authenticated-orcid":false,"given":"Irep","family":"Uras","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Institute of Health Sciences Acibadem Mehmet Ali Aydinlar University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6460-4151","authenticated-orcid":false,"given":"Merve","family":"Karayel\u2010Basar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Institute of Health Sciences Acibadem Mehmet Ali Aydinlar University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-5741","authenticated-orcid":false,"given":"Betul","family":"Sahin","sequence":"additional","affiliation":[{"name":"Acibadem Labmed Clinical Laboratories  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-7351","authenticated-orcid":false,"given":"Ahmet Tarik","family":"Baykal","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Acibadem Mehmet Ali Aydinlar University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002750"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101662\u2010x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010017\u20100946\u2010y"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132814"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10441"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270502"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"e_1_2_7_9_1","volume-title":"World Alzheimer Report 2021: Journey through the Diagnosis of Dementia","author":"Gauthier S","year":"2021"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101\u2010015\u20109440\u20102"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20103341\u20109_10"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010018\u20101199\u2010z"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010019\u20100089\u2010y"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2788"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04733"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201700173"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205016666190730155926"},{"key":"e_1_2_7_18_1","volume-title":"Metabolite Imaging by Mass Spectrometry: A New Discovery Tool","author":"Walker HJ","year":"2021"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9070135"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010017\u20100231\u20107"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597\u2010021\u201001054\u2010y"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-815854-8.00013-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12110"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/adr\u2010170049"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858408315655"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro\u20102019\u20100058"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010804766\u20108.00013\u20103"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.04.002"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030908"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00025"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12612"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527316666170113120853"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010022\u201000749\u2010z"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010017\u20100533\u20103"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093158"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00255"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313168"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2016.117"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072\u2010199403000\u201000012"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2012.13.6.674"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.09.001"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/114.3.1363"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25317"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.08.013"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201079344\u20105"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.713726"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105404"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00088"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00778"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(15)70016\u20105.Neuroinflammation"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.07.028"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002759"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905529106"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.11.093"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2010.12.012"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010130476"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-47093-1"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.63"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr400743a"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003\u20102697(02)00386\u2010X"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010017\u20100477\u2010x"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010014\u20108345\u2010z"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1mo00440a"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.04.054"},{"key":"e_1_2_7_65_1","doi-asserted-by":"crossref","unstructured":"RessomHW VargheseRS GoldmanR.Computational methods for analysis of MALDI\u2010TOF spectra to discover peptide serum biomarkers.The Protein Protocols Handbook.Springer;2009:1175\u20101183.https:\/\/doi.org\/10.1007\/978\u20101\u201059745\u2010198\u20107_125","DOI":"10.1007\/978-1-59745-198-7_125"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201025817\u20107"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpps.65"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1322"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114111"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666210827152914"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.5135"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12523"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010022\u201000919\u20106"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.09.016"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12093"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010019\u20100091\u20104"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01556"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201011\u20100023"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv128"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.3.1.7483"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.581767"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22412"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2019.01.027"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00004"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1860038"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u20107091\u20106262\u20100_23"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2006.04113.x"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.4061\/2010\/604792"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582\u20104934.2011.01394.x"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13082"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1990747816030053"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6254"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010190652"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017\u2010013\u20108257\u20107.SUMO"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep07190"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1836\u201012.2012"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527313666140806124850"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.05.006"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10225281"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.04.045.Genetic"},{"key":"e_1_2_7_101_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122954"},{"key":"e_1_2_7_102_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx352"},{"key":"e_1_2_7_103_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010141266"},{"key":"e_1_2_7_104_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.143948"},{"key":"e_1_2_7_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2016.11.006"},{"key":"e_1_2_7_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.06.002"},{"key":"e_1_2_7_107_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010018\u20100397\u20104"},{"key":"e_1_2_7_108_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010017\u20101691\u20100.Proteomic"},{"key":"e_1_2_7_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2019.06.005"},{"key":"e_1_2_7_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.08.006.An"},{"key":"e_1_2_7_111_1","doi-asserted-by":"publisher","DOI":"10.1159\/000105158"},{"key":"e_1_2_7_112_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0132\u201016.2016"},{"key":"e_1_2_7_113_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102010\u20101326"},{"key":"e_1_2_7_114_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702\u2010014\u20101320\u20101"},{"key":"e_1_2_7_115_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12089"},{"key":"e_1_2_7_116_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.580030"},{"key":"e_1_2_7_117_1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.02.22.20026609"},{"key":"e_1_2_7_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2016.07.032"},{"key":"e_1_2_7_119_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010131280"},{"key":"e_1_2_7_120_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.476689"},{"key":"e_1_2_7_121_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010130428"},{"key":"e_1_2_7_122_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092603"},{"key":"e_1_2_7_123_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/435203"},{"key":"e_1_2_7_124_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH\u201028.43"},{"key":"e_1_2_7_125_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010131685"},{"key":"e_1_2_7_126_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2019.0611"},{"key":"e_1_2_7_127_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8197085"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13008","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.13008","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:47:07Z","timestamp":1759938427000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.13008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,18]]},"references-count":126,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/alz.13008"],"URL":"https:\/\/doi.org\/10.1002\/alz.13008","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,18]]},"assertion":[{"value":"2022-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}