{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:09:27Z","timestamp":1792030167195,"version":"4.4.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870826"],"award-info":[{"award-number":["81870826"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2020C03020"],"award-info":[{"award-number":["2020C03020"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["neurotherapeuticsjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurotherapeutics"],"published-print":{"date-parts":[[2023,3]]},"DOI":"10.1007\/s13311-022-01316-6","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T13:13:59Z","timestamp":1669295639000},"page":"452-463","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"title":["Metformin Attenuates Tau Pathology in Tau-Seeded PS19 Mice"],"prefix":"10.1016","volume":"20","author":[{"given":"Shuai","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaicheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8099-7407","authenticated-orcid":false,"given":"Baorong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1007\/s13311-022-01316-6_bib1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.cell.2012.02.040","article-title":"Alzheimer mechanisms and therapeutic strategies","volume":"148","author":"Huang","year":"2012","journal-title":"Cell"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jalz.2007.11.008","article-title":"The amyloid cascade hypothesis","volume":"4","author":"Korczyn","year":"2008","journal-title":"Alzheimers Dement"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","article-title":"Staging of Alzheimer's disease-related neurofibrillary changes","volume":"16","author":"Braak","year":"1995","journal-title":"Neurobiol Aging"},{"issue":"4","key":"10.1007\/s13311-022-01316-6_bib4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrn2786","article-title":"Prion-like mechanisms in neurodegenerative diseases","volume":"11","author":"Frost","year":"2010","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib6","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1001\/jamaneurol.2013.1453","article-title":"Mechanisms of protein seeding in neurodegenerative diseases","volume":"70","author":"Walker","year":"2013","journal-title":"JAMA Neurol"},{"issue":"10","key":"10.1007\/s13311-022-01316-6_bib7","doi-asserted-by":"crossref","first-page":"a024372","DOI":"10.1101\/cshperspect.a024372","article-title":"The prion-like behavior of assembled tau in transgenic mice","volume":"7","author":"Clavaguera","year":"2017","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"4","key":"10.1007\/s13311-022-01316-6_bib8","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.neuron.2011.11.033","article-title":"Propagation of tau pathology in a model of early Alzheimer's disease","volume":"73","author":"de Calignon","year":"2012","journal-title":"Neuron"},{"issue":"5","key":"10.1007\/s13311-022-01316-6_bib9","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s00401-014-1254-6","article-title":"A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity","volume":"127","author":"Ahmed","year":"2014","journal-title":"Acta Neuropathol"},{"issue":"7","key":"10.1007\/s13311-022-01316-6_bib10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/ncb1901","article-title":"Transmission and spreading of tauopathy in transgenic mouse brain","volume":"11","author":"Clavaguera","year":"2009","journal-title":"Nat Cell Biol"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib11","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1523\/JNEUROSCI.2642-12.2013","article-title":"Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy","volume":"33","author":"Iba","year":"2013","journal-title":"J Neurosci"},{"key":"10.1007\/s13311-022-01316-6_bib12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.diabres.2016.10.024","article-title":"An updated meta-analysis of cohort studies: diabetes and risk of Alzheimer's disease","volume":"124","author":"Zhang","year":"2017","journal-title":"Diabetes Res Clin Pract"},{"issue":"1","key":"10.1007\/s13311-022-01316-6_bib13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.pharmthera.2012.07.006","article-title":"Insulin in the brain: there and back again","volume":"136","author":"Banks","year":"2012","journal-title":"Pharmacol Ther"},{"issue":"6","key":"10.1007\/s13311-022-01316-6_bib14","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.clinthera.2015.01.002","article-title":"Cognitive and functional decline in patients with mild Alzheimer dementia with or without comorbid diabetes","volume":"37","author":"Ascher-Svanum","year":"2015","journal-title":"Clin Ther"},{"issue":"1","key":"10.1007\/s13311-022-01316-6_bib15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3233\/JAD-2005-7107","article-title":"Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease\u2013is this type 3 diabetes?","volume":"7","author":"Steen","year":"2005","journal-title":"J Alzheimers Dis"},{"key":"10.1007\/s13311-022-01316-6_bib16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fendo.2018.00400","article-title":"The therapeutic potential of metformin in neurodegenerative diseases","volume":"9","author":"Rotermund","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib17","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3233\/JAD-2011-101524","article-title":"Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin","volume":"24","author":"Hsu","year":"2011","journal-title":"J Alzheimers Dis"},{"issue":"10","key":"10.1007\/s13311-022-01316-6_bib18","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/gerona\/glu073","article-title":"Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis","volume":"69","author":"Cheng","year":"2014","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"18","key":"10.1007\/s13311-022-01316-6_bib19","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1212\/WNL.0000000000004586","article-title":"Metformin vs sulfonylurea use and risk of dementia in US veterans aged >\/=65 years with diabetes","volume":"89","author":"Orkaby","year":"2017","journal-title":"Neurology"},{"key":"10.1007\/s13311-022-01316-6_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2015.12.012","article-title":"Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL\/6J mice","volume":"301","author":"Allard","year":"2016","journal-title":"Behav Brain Res"},{"key":"10.1007\/s13311-022-01316-6_bib21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neuropharm.2015.07.023","article-title":"Antidiabetic drugs restore abnormal transport of amyloid-beta across the blood-brain barrier and memory impairment in db\/db mice","volume":"101","author":"Chen","year":"2016","journal-title":"Neuropharmacology"},{"issue":"11\u201312","key":"10.1007\/s13311-022-01316-6_bib22","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.lfs.2012.08.017","article-title":"Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats","volume":"91","author":"Pintana","year":"2012","journal-title":"Life Sci"},{"key":"10.1007\/s13311-022-01316-6_bib23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13024-016-0082-7","article-title":"Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy","volume":"11","author":"Barini","year":"2016","journal-title":"Mol Neurodegener"},{"key":"10.1007\/s13311-022-01316-6_bib24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.expneurol.2018.09.008","article-title":"Metformin attenuates diabetes-induced tau hyperphosphorylation in vitro and in vivo by enhancing autophagic clearance","volume":"311","author":"Chen","year":"2019","journal-title":"Exp Neurol"},{"issue":"1","key":"10.1007\/s13311-022-01316-6_bib25","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13195-020-00761-9","article-title":"Metformin attenuates plaque-associated tau pathology and reduces amyloid-beta burden in APP\/PS1 mice","volume":"13","author":"Chen","year":"2021","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"10.1007\/s13311-022-01316-6_bib26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nm.4443","article-title":"Amyloid-beta plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation","volume":"24","author":"He","year":"2018","journal-title":"Nat Med"},{"issue":"10","key":"10.1007\/s13311-022-01316-6_bib27","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jalz.2016.01.014","article-title":"Hyperphosphorylation determines both the spread and the morphology of tau pathology","volume":"12","author":"Hu","year":"2016","journal-title":"Alzheimers Dement"},{"issue":"3","key":"10.1007\/s13311-022-01316-6_bib28","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3109\/10409238.2016.1143913","article-title":"PP2A as a master regulator of the cell cycle","volume":"51","author":"Wlodarchak","year":"2016","journal-title":"Crit Rev Biochem Mol Biol"},{"issue":"50","key":"10.1007\/s13311-022-01316-6_bib29","doi-asserted-by":"crossref","first-page":"21830","DOI":"10.1073\/pnas.0912793107","article-title":"Biguanide metformin acts on tau phosphorylation via mTOR\/protein phosphatase 2A (PP2A) signaling","volume":"107","author":"Kickstein","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1007\/s13311-022-01316-6_bib30","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1038\/ncomms9490","article-title":"Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain","volume":"6","author":"Takeda","year":"2015","journal-title":"Nat Commun"},{"key":"10.1007\/s13311-022-01316-6_bib31","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fnagi.2019.00034","article-title":"Pathological tau from Alzheimer's brain induces site-specific hyperphosphorylation and SDS- and reducing agent-resistant aggregation of tau in vivo","volume":"11","author":"Miao","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"10.1007\/s13311-022-01316-6_bib32","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3389\/fnagi.2020.00265","article-title":"Mechanisms of pathogenic tau and A\u03b2 protein spreading in Alzheimer's disease","volume":"12","author":"D'Errico","year":"2020","journal-title":"Front Aging Neurosci."},{"issue":"2","key":"10.1007\/s13311-022-01316-6_bib33","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3233\/JAD-150493","article-title":"Metformin in amnestic mild cognitive impairment: results of a pilot randomized placebo controlled clinical trial","volume":"51","author":"Luchsinger","year":"2016","journal-title":"J Alzheimers Dis"},{"issue":"5","key":"10.1007\/s13311-022-01316-6_bib34","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/j.1532-5415.2012.03916.x","article-title":"Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study","volume":"60","author":"Imfeld","year":"2012","journal-title":"J Am Geriatr Soc"},{"issue":"5","key":"10.1007\/s13311-022-01316-6_bib35","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.diabet.2016.03.008","article-title":"Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"42","author":"Chapman","year":"2016","journal-title":"Diabetes Metab"},{"issue":"4","key":"10.1007\/s13311-022-01316-6_bib36","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.jdiacomp.2017.01.013","article-title":"Differential effects of metformin on age related comorbidities in older men with type 2 diabetes","volume":"31","author":"Wang","year":"2017","journal-title":"J Diabetes Complications"}],"container-title":["Neurotherapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-022-01316-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13311-022-01316-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923000910?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923000910?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-022-01316-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:34:46Z","timestamp":1761806086000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1878747923000910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["S1878747923000910"],"URL":"https:\/\/doi.org\/10.1007\/s13311-022-01316-6","relation":{},"ISSN":["1878-7479"],"issn-type":[{"value":"1878-7479","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metformin Attenuates Tau Pathology in Tau-Seeded PS19 Mice","name":"articletitle","label":"Article Title"},{"value":"Neurotherapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1007\/s13311-022-01316-6","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2022 The Author(s). Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}