{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:41:02Z","timestamp":1790959262123,"version":"4.1.0"},"reference-count":83,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proteome profile changes in Alzheimer's disease (AD) brains have been reported. However, it is unclear whether they represent a continuous process, or whether there is a sequential involvement of distinct proteins. To address this question, we used mass spectrometry. We analyzed soluble, dispersible, sodium dodecyl sulfate, and formic acid fractions of neocortex homogenates (mainly Brodmann area 17\u201019) from 18 pathologically diagnosed preclinical AD, 17 symptomatic AD, and 18 cases without signs of neurodegeneration. By doing so, we identified four groups of AD\u2010related proteins being changed in levels in preclinical and symptomatic AD cases: early\u2010responding, late\u2010responding, gradually\u2010changing, and fraction\u2010shifting proteins. Gene ontology analysis of these proteins and all known AD\u2010risk\/causative genes identified vesicle endocytosis and the secretory pathway\u2010related processes as an early\u2010involved AD component. In conclusion, our findings suggest that subtle changes involving the secretory pathway and endocytosis precede severe proteome changes in symptomatic AD as part of the preclinical phase of AD. The respective early\u2010responding proteins may also contribute to synaptic vesicle cycle alterations in symptomatic AD.<\/jats:p>","DOI":"10.1002\/alz.12345","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T13:36:42Z","timestamp":1618839402000},"page":"946-958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease"],"prefix":"10.1002","volume":"17","author":[{"given":"Xiaohang","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory for Neuropathology Department of Imaging and Pathology KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Leuven Brain Institute (LBI) KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos C.","family":"Tsolis","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Bacteriology Rega Institute Department of Microbiology and Immunology KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta J.","family":"Koper","sequence":"additional","affiliation":[{"name":"Laboratory for Neuropathology Department of Imaging and Pathology KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Leuven Brain Institute (LBI) KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Laboratory for the Research of Neurodegenerative Diseases Department of Neurosciences KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Center for Brain and Disease Research VIB  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Ronisz","sequence":"additional","affiliation":[{"name":"Laboratory for Neuropathology Department of Imaging and Pathology KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Leuven Brain Institute (LBI) KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Ospitalieri","sequence":"additional","affiliation":[{"name":"Laboratory for Neuropathology Department of Imaging and Pathology KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Leuven Brain Institute (LBI) KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.F.","family":"von Arnim","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm  Ulm Germany"},{"name":"Department of Geriatrics University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Department of Neurology UZ Leuven (University Hospitals Leuven)  Leuven Belgium"},{"name":"Laboratory for Cognitive Neurology Department of Neurosciences KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tousseyn","sequence":"additional","affiliation":[{"name":"Department of Pathology UZ Leuven (University Hospitals Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Scheuerle","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastassios","family":"Economou","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Bacteriology Rega Institute Department of Microbiology and Immunology KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Carpentier","sequence":"additional","affiliation":[{"name":"BIOMED facility for SYstems BIOlogy based MAss spectrometry KU Leuven (University of Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Otto","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-1075","authenticated-orcid":false,"given":"Dietmar Rudolf","family":"Thal","sequence":"additional","affiliation":[{"name":"Laboratory for Neuropathology Department of Imaging and Pathology KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Leuven Brain Institute (LBI) KU Leuven (University of Leuven)  Leuven Belgium"},{"name":"Department of Pathology UZ Leuven (University Hospitals Leuven)  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.03.001"},{"key":"e_1_2_8_3_1","first-page":"146","article-title":"\u00dcber eine eigenartige Erkrankung der Hirnrinde","volume":"64","author":"Alzheimer A","year":"1907","journal-title":"Allg Zschr Psych"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38495-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.12.4245"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt362"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1791"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7558-7_18"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0815-6"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201100068"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201600057"},{"key":"e_1_2_8_16_1","first-page":"60\u201072 e4","article-title":"A multi\u2010network approach identifies protein\u2010specific co\u2010expression in asymptomatic and symptomatic Alzheimer's sisease","volume":"4","author":"Seyfried NT","year":"2017","journal-title":"Cell Syst"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.11.002"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104509"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(97)90255-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.35.22364"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079469"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04533"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703793104"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1782"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.12.032"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.089110"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010454"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1895-y"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.029"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/proteomes7030030"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00004"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr3001546"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr401202d"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0254-9"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.04.031"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sageke.2006.6.re1"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100346"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.1424"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.04.011"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww023"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1709-7"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1691-0"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042823"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.05263-11"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(97)00233-7"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181e24adb"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00122"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2002.tb00457.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2019.08.005"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90696-3"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02251-6"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108420"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0789-4"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0305-1846.2000.00291.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004019900178"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.14.2355"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.3.777"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207763"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2015.02.004"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2004.12.002"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07761"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02053-5"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02114-9"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.4161\/pri.3.2.9135"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059554"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300503"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.12.1287"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0871-6"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.9.1159"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00127-7"},{"key":"e_1_2_8_73_1","first-page":"19012021","article-title":"Common variants in Alzheimer's disease: novel association of six genetic variants with AD and risk stratification by polygenic risk scores","author":"Rojas I","year":"2020","journal-title":"medRxiv"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00170-19"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2008.01256.x"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0848-6"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.913895"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/376775a0"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/353844a0"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1292-330"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12345","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12345","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T19:36:07Z","timestamp":1759865767000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":83,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/alz.12345"],"URL":"https:\/\/doi.org\/10.1002\/alz.12345","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]},"assertion":[{"value":"2020-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}