{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:44:39Z","timestamp":1790423079295,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG067063"],"award-info":[{"award-number":["R01AG067063"]}],"id":[{"id":"10.13039\/100000002","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":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      While the apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54 allele is a major risk factor for Alzheimer's disease (AD), the role of translocase of outer mitochondrial membrane 40 (\n                      <jats:italic>TOMM40<\/jats:italic>\n                      )\u2014an adjacent gene involved in mitochondrial protein import\u2014is not known.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Human brain tissue, human induced pluripotent stem cell\u2013derived neurons (iNeurons), and mice were used for study of gene expression, cholesterol metabolism, mitochondrial function, and animal cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Human brain transcriptomics showed reduced\n                      <jats:italic>TOMM40<\/jats:italic>\n                      expression that correlated with cholesterol regulatory gene expression, amyloid burden, and clinical AD diagnosis. In human iNeurons,\n                      <jats:italic>TOMM40<\/jats:italic>\n                      knockdown (KD) disrupted mitochondria\u2013endoplasmic reticulum contact sites (MERCs), causing mitochondrial dysfunction and promoting reactive oxygen species that led to activation of liver X receptor beta (NR1H2), upregulation of\n                      <jats:italic>APOE<\/jats:italic>\n                      and low\u2010density lipoprotein receptor (\n                      <jats:italic>LDLR<\/jats:italic>\n                      ), and increased cellular cholesterol and amyloid beta (A\u03b2)42 independent of\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54. Consistently,\n                      <jats:italic>Tomm40<\/jats:italic>\n                      KD in mice induced increased brain cholesterol, A\u03b242 content, and impaired memory.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>TOMM40\u00a0is a novel mediator of AD pathology through dual effects on MERCs that regulate cholesterol homeostasis and mitochondrial function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71306","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:47:41Z","timestamp":1775728061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>TOMM40<\/i>\n                    suppression promotes neuronal cholesterol imbalance and molecular and behavioral phenotypes of Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Neil V.","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California, San Francisco  San Francisco California USA"},{"name":"Department of Medicine University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Li","sequence":"additional","affiliation":[{"name":"Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Simms","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Neurological Disease Gladstone Institutes  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsey","family":"Dinh","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Neurological Disease Gladstone Institutes  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Cell Biology University of California, Berkeley  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob H.","family":"Oei","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Cell Biology University of California, Berkeley  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein N.","family":"Yassine","sequence":"additional","affiliation":[{"name":"Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Krauss","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California, San Francisco  San Francisco California USA"},{"name":"Department of Medicine University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02931-w"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00740-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307023"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263195"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae028"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.03.015"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.09.617477"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24044085"},{"issue":"1","key":"e_1_2_11_11_1","first-page":"12","article-title":"The broad impact of TOM40 on neurodegenerative diseases in aging","volume":"1","author":"Gottschalk WK","year":"2014","journal-title":"J Parkinsons Dis Alzheimers Dis"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-018-0584-7"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.102056"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219668.47116.e6"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000152982.47274.9E"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.039"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1504393112"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(97)00111-3"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003058"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092177"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2011.03526.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.3.378"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199911000-00004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.253443"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092195"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.2.507"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.179564"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2019.158546"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01732-3"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.09.007"},{"issue":"96","key":"e_1_2_11_34_1","article-title":"Use of the open field maze to measure locomotor and anxiety\u2010like behavior in mice","author":"Seibenhener ML","year":"2015","journal-title":"J Vis Exp"},{"issue":"22","key":"e_1_2_11_35_1","first-page":"1088","article-title":"Elevated plus maze for mice","author":"Komada M","year":"2008","journal-title":"J Vis Exp"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.05.005"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(96)00058-9"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-00721-2"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-009-8109-7"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.5607\/en23006"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2231"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-09270-1"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-110743"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.08.005"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01127-y"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01249-0"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040173"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1400-19.2019"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00802-7"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100051"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135218"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.918691"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220518"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00252"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14585"},{"issue":"1","key":"e_1_2_11_57_1","first-page":"S253","article-title":"Abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease","volume":"33","author":"Zhu X","year":"2013","journal-title":"J Alzheimers Dis"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112785"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.044"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.008"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1065-09.2009"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-0933"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(03)00025-7"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.155"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12362"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2013.15.4\/hjahn"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2013.07.013"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(07)63039-8"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-022-03123-4"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01010.x"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-01873-x"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71306","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:03:18Z","timestamp":1783321398000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":70,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/alz.71306"],"URL":"https:\/\/doi.org\/10.1002\/alz.71306","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.10.31.685963","asserted-by":"object"}]},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71306"}}