{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:25:34Z","timestamp":1773008734983,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"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":["81871714"],"award-info":[{"award-number":["81871714"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L246009"],"award-info":[{"award-number":["L246009"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Synaptic vesicle glycoprotein 2A (SV2A), a transmembrane protein widely localized to synaptic vesicles, serves as a key indicator of synaptic loss in Alzheimer's disease (AD). In this study, adeno\u2010associated virus (AAV) was injected by brain stereotactic injection technique to construct SV2A\u2010overexpressing APP\/PS1 mice, then the effects of SV2A on amyloid precursor protein (APP) degradation and its molecular mechanism were further explored in\u00a0vivo or in\u00a0vitro. Our results demonstrated that SV2A overexpression significantly reduced A\u03b2 plaque deposition in brain tissue of APP\/PS1 mice. Mechanistically, SV2A was identified as a novel APP\u2010binding protein that attenuated the amyloidogenic processing of APP by inhibiting its interaction with \u03b2\u2010site APP cleaving enzyme 1 (BACE1). Furthermore, SV2A overexpression altered the subcellular distribution of APP, shifting its localization away from the endosomal\u2010lysosomal compartments. Collectively, our findings unveil SV2A as a critical regulator of APP metabolism and propose it as a promising therapeutic target for intervening in the early pathological progression of AD.<\/jats:p>","DOI":"10.1111\/acel.70379","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:37:50Z","timestamp":1768203470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synaptic Vesicle Glycoprotein\n                    <scp>2A<\/scp>\n                    Suppresses Amyloidogenesis Beyond Its Synaptic Role: A Novel Mechanism Disrupting\n                    <scp>BACE1<\/scp>\n                    Binding and Altering\n                    <scp>APP<\/scp>\n                    Localization"],"prefix":"10.1111","volume":"25","author":[{"given":"Xiaoling","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"},{"name":"Department of Clinical Laboratory Changzhi People's Hospital of Changzhi Medical College  Changzhi Shanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-145X","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congcong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuli","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-440X","authenticated-orcid":false,"given":"Yaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Beijing Huairou Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-9797","authenticated-orcid":false,"given":"Peichang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Xuanwu Hospital, National Clinical Research Center for Geriatric Disorders Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2020.101879"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14\u201009\u201005223.1994"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.023"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010019\u201004461\u2010x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000702\u20102"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.1836"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102821"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2010.01.015"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.035"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010021\u201001569\u2010z"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009164\u20103"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(21)00066\u20101"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(06)68542\u20105"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1397"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006270"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/357500a0"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009562\u20107"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1963630"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896\u20106273(00)81046\u20106"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2252300"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000391\u2010w"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.114927"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c11511"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201045192\u20104"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010152\u2010w"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037860\u20108"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/547153a"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12582"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200573"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2306714120"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.03.024"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe6178"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010024\u201002463\u20102"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010061010\u2010113613"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000742\u2010y"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2023.05.022"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.43.2.250"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121081109"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202311670"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010020\u201000399\u2010z"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo3610"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00351"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2023.100544"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk1051"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.11.008"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202402007"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201044307\u20107"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.125393"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010022\u201001454\u20105"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201047322\u20104"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1523\/Jneurosci.4781\u201009.2010"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001431\u20106"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000611\u2010w"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2023.100835"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201004433\u2010w"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70379","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70379","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:32:12Z","timestamp":1773001932000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,11]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/acel.70379"],"URL":"https:\/\/doi.org\/10.1111\/acel.70379","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,11]]},"assertion":[{"value":"2025-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70379"}}