{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:06:17Z","timestamp":1780542377988,"version":"3.54.1"},"reference-count":90,"publisher":"Wiley","issue":"21-22","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100023885","name":"All of Us Research Program","doi-asserted-by":"publisher","award":["U24 HG012198"],"award-info":[{"award-number":["U24 HG012198"]}],"id":[{"id":"10.13039\/100023885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203149"],"award-info":[{"award-number":["203149"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["212925\/Z\/18\/Z"],"award-info":[{"award-number":["212925\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["218294"],"award-info":[{"award-number":["218294"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["3367"],"award-info":[{"award-number":["3367"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia. Many cases are diagnosed annually and there is no currently available cure. Understanding the underlying disease biology of AD through the study of molecular networks, particularly by mapping clinical variants to tissue\u2010specific interactomes and regulatory macromolecular assemblies, offers a promising avenue to elucidate altered disease pathways. In this study, we applied differential interactome analysis using a manually curated AD dataset to identify how disease\u2010associated mutations alter both transient and stable protein interactions. By focussing on variant\u2010specific associations detected in brain\u2010relevant tissues, we mapped disruptions in stable macromolecular assemblies and performed Reactome enrichment analysis to uncover perturbed pathways unique to each variant. Additionally, we explored therapeutic insights through the analysis of amyloid precursor protein (APP) physical interactors, identifying potential intervention points that influence amyloidogenic processing. Complementing protein\u2010level data, we integrated microRNA (miRNA)\u2010mediated regulatory interactions, revealing an additional layer of posttranscriptional control over key AD genes. Together, this multilayered strategy provides a framework for precision therapeutics in AD.<\/jats:p>","DOI":"10.1002\/pmic.70018","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T05:26:32Z","timestamp":1756185992000},"page":"102-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for Drug Discovery"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-198X","authenticated-orcid":false,"given":"Kalpana","family":"Panneerselvam","sequence":"first","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna Kumar","family":"Tiwari","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Licata","sequence":"additional","affiliation":[{"name":"University of Rome Tor Vergata Macro Area of Mathematical Physical and Natural Sciences  Roma Lazio Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Panni","sequence":"additional","affiliation":[{"name":"University of Calabria Department of Biology Ecology and Earth Sciences  Arcavacata di Rende Calabria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-1851","authenticated-orcid":false,"given":"Sylvie","family":"Ricard\u2010Blum","sequence":"additional","affiliation":[{"name":"Universite Lyon 1 IUT Lyon 1  Villeurbanne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucharitha","family":"Balu","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susie","family":"Huget","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jose","family":"Medina Reyes","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-6503","authenticated-orcid":false,"given":"Eliot","family":"Ragueneau","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Perfetto","sequence":"additional","affiliation":[{"name":"University of Rome La Sapienza Faculty of Mathematical Physical and Natural Sciences  Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Meldal","sequence":"additional","affiliation":[{"name":"Pfizer Institute for Pharmaceutical Materials Science  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Orchard","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Hermjakob","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute (EMBL\u2010EBI), European Molecular Biology Laboratory, Hinxton  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19942-z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr930"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1035"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh086"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200900773"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400390"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200206"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-011-0592-x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1186-9_22"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07709-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab991"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa223"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150298"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.041"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20554"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0197-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-072116-031153"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1633508100"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.13.4913"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910283"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.07.029"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.65.1.29"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.259764"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105514"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1922982"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00391"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf6548"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00154\u201018"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.10.2193"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12046"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.06.002"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac883"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-016-0462-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2181614"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3823"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23533"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.115239"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.03.008"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.733626"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.45"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90044-Y"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(97)00045-4"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2569763"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-4-3"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.05.050"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108122"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201796797"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20905206"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04205-5"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04182-9"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12166"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2021.60"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.02.004"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.03.019"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-018-0191-1"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006304"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.10.018"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.05.012"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01052-z"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-102115"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055810"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104794"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004019900165"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)89624-0"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.103869"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.05.003"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.02.043"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04640-1"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.13188\/2376\u2010922X.1000010"},{"key":"e_1_2_9_76_1","doi-asserted-by":"crossref","unstructured":"E.Ragueneau A.Shrivastava J. H.Morris N.Del\u2010Toro H.Hermjakob andP.Porras \u201cIntAct App: a Cytoscape Application for Molecular Interaction Network Visualization and Analysis\u201d (2021) https:\/\/academic.oup.com\/bioinformatics\/article\u2010abstract\/37\/20\/3684\/6271410.","DOI":"10.1093\/bioinformatics\/btab319"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb34433.x"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2014.05.031"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-01970-9"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720512799015055"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-61777-7"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01208-4"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2023.07.001"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12653"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-019-0313-z"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx727"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02311-2"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0185\u201017.2017"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8637-5"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113481"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0320-4"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.70018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:24:56Z","timestamp":1766049896000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.70018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":90,"journal-issue":{"issue":"21-22","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/pmic.70018"],"URL":"https:\/\/doi.org\/10.1002\/pmic.70018","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,25]]},"assertion":[{"value":"2025-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}