{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:40:59Z","timestamp":1761514859708,"version":"3.41.2"},"reference-count":70,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Our understanding of the pathological interactions between amyloidosis and tauopathy in Alzheimer's disease is incomplete. We sought to determine if the relative timing of the amyloidosis and tauopathy is critical for amyloid\u2010enhanced tauopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We crossed an inducible tauopathy model with two \u03b2\u2010amyloid models utilising the doxycycline\u2010repressible transgenic system to modulate timing and duration of human tau expression in the context of amyloidosis and then assessed tauopathy, amyloidosis and gliosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We combined inducible rTg4510 tau with APPswe\/PS1dE9 [Line 85 (L85)] mice to examine the interactions between A\u03b2 and tauopathy at different stages of amyloidosis. When we initially suppressed mutant human tau expression for 14\u201315\u2009months and subsequently induced tau expression for 6\u00a0months, severe amyloidosis with robust tauopathy resulted in rTg4510\/L85 but not rTg4510 mice. When we suppressed mutant tau for 7\u00a0months before inducing expression for a subsequent 6\u00a0months in another cohort of rTg4510\/L85 and rTg4510 mice, only rTg4510\/L85 mice displayed robust tauopathy. Lastly, we crossed rTg4510 mice to tet\u2010regulated APPswe\/ind [Line 107 (L107)] mice, using doxycycline to initially suppress both transgenes for 1\u00a0month before inducing expression for 5\u00a0months to model early amyloidosis. In contrast to rTg4510, rTg4510\/L107 mice rapidly developed amyloidosis, accompanied by robust tauopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that tau misfolding is exacerbated by both newly forming A\u03b2 deposits in younger brain and mature deposits in older brains. Refined use and repurposing of these models provide new tools to explore the intersection of ageing, amyloid and tauopathy and to test interventions to disrupt the amyloid cascade.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12791","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T03:08:56Z","timestamp":1642993736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TAPPing into the potential of inducible tau\/APP transgenic mice"],"prefix":"10.1111","volume":"48","author":[{"given":"Guilian","family":"Xu","sequence":"first","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"},{"name":"Evelyn F. and William L. McKnight Brain Institute University of Florida  Gainesville FL USA"},{"name":"Department of Neuroscience University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittany S.","family":"Ulm","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"},{"name":"Evelyn F. and William L. McKnight Brain Institute University of Florida  Gainesville FL USA"},{"name":"Department of Neuroscience University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Howard","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Fromholt","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian Benedict","family":"Lee","sequence":"additional","affiliation":[{"name":"Evelyn F. and William L. McKnight Brain Institute University of Florida  Gainesville FL USA"},{"name":"Department of Neuroscience University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Walker","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"},{"name":"Evelyn F. and William L. McKnight Brain Institute University of Florida  Gainesville FL USA"},{"name":"Department of Neuroscience University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Borchelt","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"},{"name":"Evelyn F. and William L. McKnight Brain Institute University of Florida  Gainesville FL USA"},{"name":"Department of Neuroscience University of Florida  Gainesville FL USA"},{"name":"SantaFe HealthCare Alzheimer's Disease Research Center, College of Medicine University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0004-6597","authenticated-orcid":false,"given":"Jada","family":"Lewis","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville FL USA"},{"name":"Evelyn F. and William L. McKnight Brain Institute University of Florida  Gainesville FL USA"},{"name":"Department of Neuroscience University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13632"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12192"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02004-0"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14079"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.79"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.06.030"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170228"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2013.833510"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2019.10.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0231-7"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3279-05.2005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/78078"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113694"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/31508"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7737"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410430617"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058189"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.080175"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00434-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3672-12.2013"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12082"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4443"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062097"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh019"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020355"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100710200"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308476"},{"key":"e_1_2_11_32_1","first-page":"189.9","article-title":"Alzheimer plaques and tangles: a controlled and enhanced silver staining method","volume":"13","author":"Campbell SK","year":"1987","journal-title":"Soc Neurosci Abstr"},{"issue":"1","key":"e_1_2_11_33_1","first-page":"1","article-title":"Silver staining of Alzheimer's neurofibrillary changes by means of physical development","volume":"19","author":"Gallyas F","year":"1971","journal-title":"Acta Morphol Acad Sci Hung"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0200-2"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970415)48:2<128::AID-JNR5>3.0.CO;2-E"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227819"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)91264-Q"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490390607"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90851-5"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.32.5.1208"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-174"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2017.04.007"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80974-5"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi236"},{"issue":"195","key":"e_1_2_11_45_1","first-page":"e1","article-title":"Ex vivo cultures of microglia from young and aged rodent brain reveal age\u2010related changes in microglial function","volume":"33","author":"Njie EG","year":"2012","journal-title":"Neurobiol Aging"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.05.009"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00194-7"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt121"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1895-y"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045881"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-110161"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100423"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2520542.x"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.11.1803"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.12.1220"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0252-9"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4251-12.2013"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-28"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMT.S2035"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1256-19.2019"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080764"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0893-12.2012"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10428-1"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.05.027"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0199-x"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-141754"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.03.011"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy117"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.3.728"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24454"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.029"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12791","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.12791","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T10:10:07Z","timestamp":1693131007000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":70,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/nan.12791"],"URL":"https:\/\/doi.org\/10.1111\/nan.12791","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"type":"print","value":"0305-1846"},{"type":"electronic","value":"1365-2990"}],"subject":[],"published":{"date-parts":[[2022,3,8]]},"assertion":[{"value":"2021-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12791"}}