{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:29:08Z","timestamp":1792016948155,"version":"4.4.0"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["K12GM088021"],"award-info":[{"award-number":["K12GM088021"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["IRACDA"],"award-info":[{"award-number":["IRACDA"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["P51OD011107"],"award-info":[{"award-number":["P51OD011107"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RF1NS083704\u201005A1"],"award-info":[{"award-number":["RF1NS083704\u201005A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS083704"],"award-info":[{"award-number":["R01NS083704"]}],"id":[{"id":"10.13039\/100000065","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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Pathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer's disease (AD), and correlates with cognitive decline. A rapid surge in tau\u2010targeted approaches via anti\u2010sense oligonucleotides, active\/passive immunotherapies suggests that targeting p\u2010Tau is a viable strategy against tauopathies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHOD<\/jats:title>\n                    <jats:p>We describe a multi\u2010species validation of our previously described Q\u00df virus\u2010like particle (VLP)\u2013based vaccine technology targeting phosphorylated tau on threonine 181 (pT181\u2010Q\u00df).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Two vaccine doses of pT181\u2010Q\u00df, without any adjuvants, elicited robust antibody responses in two different mouse models of tauopathy (PS19 and hTau) and rhesus macaques. In mouse models, vaccination reduced AT180+ hyperphosphorylated, Sarkosyl insoluble, Gallyas silver positive tau, inflammasomes\/neuroinflammation, and improved recognition memory and motor function without inducing adverse T\u2010cell activation. Anti\u2010pT181 antibodies are reactive to pTau in human AD brains, engage pT181+ tau in human brain lysates, and are central nervous system bioavailable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our results suggest the translational utility of pT181\u2010Q\u00df against tauopathies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Icosahedral display of phosphorylated tau at threonine 181 (pT181) Q\u00df virus\u2010like particle surface (\u201cpT181\u2010Q\u00df\u201d vaccine) induces a robust immune response in mice and in non\u2010human primates (NHPs)<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>pT181\u2010Q\u00df vaccination reduces pathological tau (pTau) and brain atrophy, and improves memory and motor function in PS19 and hTau mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>pT181\u2010Q\u00df vaccination\u2013induced immunoglobulin Gs (IgGs) are safe, Th2 skewed (anti\u2010inflammatory), specific to pTau in human AD brain, and efficiently engage pT181 in NHPs and human brain lysate.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            pT181\n                            <jats:sup>+<\/jats:sup>\n                            tau in human plasma correlates with the neurofilament light in subjects with mild cognitive impairment (MCI)\u2014suggesting the presence of pT181\u2010Q\u00df vaccine target in the early disease state.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70101","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T23:48:26Z","timestamp":1743292106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting of phosphorylated tau at threonine 181 by a Q\u03b2 virus\u2010like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques"],"prefix":"10.1002","volume":"21","author":[{"given":"Nicole M.","family":"Maphis","sequence":"first","affiliation":[{"name":"Department of Neuroscience 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hulse","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne","family":"Peabody","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somayeh","family":"Dadras","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelin J","family":"Whelpley","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manas","family":"Kandath","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Radiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Hobson","sequence":"additional","affiliation":[{"name":"Center for Memory and Aging 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Thompson","sequence":"additional","affiliation":[{"name":"Center for Memory and Aging 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suttinee","family":"Poolsup","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Beckman","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P","family":"Ott","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer W.","family":"Watanabe","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie L.","family":"Usachenko","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen K","family":"Van Rompay","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Morrison","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Selwyn","sequence":"additional","affiliation":[{"name":"Department of Radiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Center for Memory and Aging 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Knoefel","sequence":"additional","affiliation":[{"name":"Center for Memory and Aging 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Chackerian","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Bhaskar","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology 1 University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0557-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.029"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1069411"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00586-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12236"},{"key":"e_1_2_9_7_1","first-page":"1797","article-title":"Plasma p\u2010tau231 and p\u2010tau217 as state markers of amyloid\u2010beta pathology in preclinical Alzheimer's disease","volume":"28","author":"Mila\u2010Aloma M","year":"2022","journal-title":"Nat Med"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13737"},{"key":"e_1_2_9_9_1","first-page":"236","article-title":"Preclinical and clinical development of ABBV\u20108E12, a humanized anti\u2010tau antibody, for treatment of Alzheimer's disease and other tauopathies","volume":"4","author":"West T","year":"2017","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-018-0436-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072301"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-019-0118-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12010074"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00897-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2006.258"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.277061"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301440110"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0387-15.2015"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05321.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170810"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109720"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00069"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4637-04.2005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01879.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.6.1179"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.09.044"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines4010003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv081"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02211-1"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221146127"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2024.102916"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-081022-021207"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1769-z"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25158"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01749-w"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.022"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1999.0279"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1065-09.2009"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.05.004"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019567"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.05.010"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.09.044"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00743-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-020-00274-4"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0755-1"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114408"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00075"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12179"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12385"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-199851"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11484-E"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24988"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.04.187"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100423"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00293315"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1632-3"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-023-02659-w"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.01.006"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00416-z"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-024-00904-1"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.08.023"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0221-y"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.805169"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2024.02.014"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70101","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70101","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:21:36Z","timestamp":1789554096000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/alz.70101"],"URL":"https:\/\/doi.org\/10.1002\/alz.70101","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"2024-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70101"}}