{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:46:07Z","timestamp":1790718367320,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000359","name":"Royal Historical Society","doi-asserted-by":"publisher","award":["P30AG072973"],"award-info":[{"award-number":["P30AG072973"]}],"id":[{"id":"10.13039\/501100000359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000359","name":"Royal Historical Society","doi-asserted-by":"publisher","award":["R01AG061194"],"award-info":[{"award-number":["R01AG061194"]}],"id":[{"id":"10.13039\/501100000359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000359","name":"Royal Historical Society","doi-asserted-by":"publisher","award":["R01AG060733"],"award-info":[{"award-number":["R01AG060733"]}],"id":[{"id":"10.13039\/501100000359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020465","name":"Thompson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32AG078114"],"award-info":[{"award-number":["T32AG078114"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's disease (AD) features changes in mitochondrial structure and function. Investigators debate where to position mitochondrial pathology within the chronology and context of other AD features.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>To address whether mitochondrial dysfunction alters AD\u2010implicated genes and proteins, we treated SH\u2010SY5Y cells and induced pluripotent stem cell (iPSC)\u2010derived neurons with chloramphenicol, an antibiotic that inhibits mtDNA\u2010generated transcript translation. We characterized adaptive, AD\u2010associated gene, and AD\u2010associated protein responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>SH\u2010SY5Y cells and iPSC neurons responded to mtDNA transcript translation inhibition by increasing mtDNA copy number and transcription. Nuclear\u2010expressed respiratory chain mRNA and protein levels also changed. There were AD\u2010consistent concordant and model\u2010specific changes in amyloid precursor protein, beta amyloid, apolipoprotein E, tau, and \u03b1\u2010synuclein biology.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Primary mitochondrial dysfunction induces compensatory organelle responses, changes nuclear gene expression, and alters the biology of AD\u2010associated genes and proteins in ways that may recapitulate brain aging and AD molecular phenomena.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>In AD, mitochondrial dysfunction could represent a disease cause or consequence.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We inhibited mitochondrial translation in human neuronal cells and neurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Mitochondrial and nuclear gene expression shifted in adaptive\u2010consistent patterns.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>APP, A\u03b2, APOE, tau, and \u03b1\u2010synuclein biology changed in AD\u2010consistent patterns.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Mitochondrial stress creates an environment that promotes AD pathology.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14275","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T10:10:23Z","timestamp":1729678223000},"page":"8429-8443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibiting mtDNA transcript translation alters Alzheimer's disease\u2010associated biology"],"prefix":"10.1002","volume":"20","author":[{"given":"Alexander P.","family":"Gabrielli","sequence":"first","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"},{"name":"Cell Biology and Physiology University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesya","family":"Novikova","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amol","family":"Ranjan","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowan","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ernst","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanushki","family":"Abeykoon","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anysja","family":"Roberts","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Kopp","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton","family":"Mansel","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlan","family":"Qiao","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton R.","family":"Lysaker","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"},{"name":"Biochemistry and Molecular Biology, University of Kansas Medical Center Kansas City Kansas USA"},{"name":"Neurology the University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian W.","family":"Wiedling","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"},{"name":"Neurology the University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"},{"name":"Biochemistry and Molecular Biology, University of Kansas Medical Center Kansas City Kansas USA"},{"name":"Neurology the University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell H.","family":"Swerdlow","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center Kansas City Kansas USA"},{"name":"Cell Biology and Physiology University of Kansas Medical Center Kansas City Kansas USA"},{"name":"Biochemistry and Molecular Biology, University of Kansas Medical Center Kansas City Kansas USA"},{"name":"Neurology the University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4149"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170585"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-011-9272-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90609-V"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-221286"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2003.12.045"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh140"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903563106"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2009.08.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.4.918"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2020.01.008"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200286"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200008)48:2<148::AID-ANA3>3.0.CO;2-7"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-221177"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0116-19.2019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12461"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2012.02.023"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67051897.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq085"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.03.003"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0037"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00025.2007"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg284"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00664-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt211"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308298200"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40438-4"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1542\/pir.25-8-284"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00729-05"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051056"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14420-x"},{"key":"e_1_2_8_35_1","first-page":"522","article-title":"Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect","volume":"5","author":"Demetrius LA","year":"2014","journal-title":"Front Physiol"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.40.110405.090613"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030275"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076128"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160818224"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02792-w"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.026"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0228-7"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-023-00776-9"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00851-3"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.04.010"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85779"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01568-1"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113613"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.12.4245"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104905"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01617-5"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12084"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.67"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0711-0"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0320-x"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12814"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21327"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2007.03.005"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00495-8"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12812"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709259105"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14021"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.015"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1997.2647"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(97)00278-7"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-09-03017.2001"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.09.83"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215280"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1626"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02380-2"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-221153"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2016.12.017"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:27:36Z","timestamp":1759922856000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,23]]},"references-count":72,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/alz.14275"],"URL":"https:\/\/doi.org\/10.1002\/alz.14275","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,23]]},"assertion":[{"value":"2024-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}