{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:51:27Z","timestamp":1774356687077,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970536"],"award-info":[{"award-number":["31970536"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370891"],"award-info":[{"award-number":["32370891"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303431"],"award-info":[{"award-number":["82303431"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M730688"],"award-info":[{"award-number":["2023M730688"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The amyloid precursor protein (APP) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). While the production of Amyloid beta (A\u03b2) has traditionally been considered the primary cause of AD, the role of the APP intracellular domain (AICD) remains largely elusive. In this study, we established a novel model in the adult fly wing by expressing human APP, recapitulating AD\u2010associated axon degeneration. Using this model, we discovered that ectopic APP expression in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    wing margin neurons led to age\u2010dependent axon degeneration. APP's effect depended on AICD production, and AICD overexpression alone was sufficient to induce axon degeneration in adult wings. Further investigations indicated that APP\u2010 or AICD\u2010induced axon degeneration could be alleviated by blocking autophagy, but not apoptosis. Additionally, we identified a FoxO\/Snail\u2013Atg1 axis as an essential mediator of APP\/AICD\u2010induced autophagy\u2010dependent axon degeneration. Finally, we demonstrated that administration of chloroquine, an autophagy inhibitor, effectively ameliorates APP\u2010 or AICD\u2010induced axon degeneration. Our findings provide crucial insights into how APP induces autophagy\u2010dependent axon degeneration through AICD production, laying a foundation for future investigations into AD pathogenesis.\n                  <\/jats:p>","DOI":"10.1111\/acel.70301","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T07:31:27Z","timestamp":1763969487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>APP<\/scp>\n                    Induces\n                    <scp>AICD<\/scp>\n                    \u2010Mediated Autophagy\u2010Dependent Axon Degeneration"],"prefix":"10.1111","volume":"25","author":[{"given":"Jingjing","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruihong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luming","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elleen","family":"Xue","sequence":"additional","affiliation":[{"name":"Mathey College Princeton University  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Rehabilitation Hospital of Shanghai, School of Medicine Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongwei","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-8414","authenticated-orcid":false,"given":"Lei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00809-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1438807"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfac075"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058783"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-009-8104-z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00139"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2020.1758732"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812840"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.01.065"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2016.05.002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959-4388(91)90067-H"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00496-2"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.116"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2118285119"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0016-19.2019"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4521-10.2010"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.07.031"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4748"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3922"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14355"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90024-8"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1805-09.2009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003664"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07767"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.08.042"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.019265"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113613"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00434-3"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2104-y"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep16816"},{"issue":"5","key":"e_1_2_10_32_1","first-page":"S425","article-title":"Cerebrospinal Fluid BACE1 Activity and Markers of Amyloid Precursor Protein Metabolism and Axonal Degeneration in Alzheimer's Disease","volume":"10","author":"Perneczky R.","year":"2014","journal-title":"Alzheimer's & Dementia"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1098703"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407101200"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11049"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn240"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80215-2"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-18-07793.1999"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201108111"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.196"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200376"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16411-5"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.28802"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.05.010"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900461200"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2014-0076"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.082487"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13070"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001708"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:55:49Z","timestamp":1774353349000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,23]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/acel.70301"],"URL":"https:\/\/doi.org\/10.1111\/acel.70301","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,23]]},"assertion":[{"value":"2023-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70301"}}