{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:51:27Z","timestamp":1791337887521,"version":"4.3.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disease in which extracellular aggregates of the amyloid beta (A\u03b2) peptide precede widespread intracellular inclusions of the microtubule\u2010associated protein tau. The autosomal dominant form of AD requires mutations that increase production or aggregation of the A\u03b2 peptide. This has led to the hypothesis that amyloid deposition initiates downstream responses that lead to the hyperphosphorylation and aggregation of tau.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Here we use a novel approach, somatic gene transfer via intravenous adeno\u2010associated virus (AAV), to further explore the effects of pre\u2010existing amyloid deposits on tauopathy. APP+PS1 mice, which develop amyloid deposits at 3 to 6 months of age, and non\u2010transgenic littermates were injected at 8 months of age intravenously with AAV\u2010PHP.eB encoding P301L human tau. Tissue was collected at 13 months and tauopathy was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Total human tau expression was observed to be relatively uniform throughout the brain, reflecting the vascular route of AAV administration. Phospho\u2010tau deposition was not equal across brain regions and significantly increased in APP+PS1 mice compared to non\u2010transgenic controls. Interestingly, the rank order of phospho\u2010tau deposition of affected brain regions in both genotypes paralleled the rank order of amyloid plaque deposits in APP+PS1 mice. We also observed significantly increased\n                      <jats:italic>MAPT<\/jats:italic>\n                      RNA expression in APP+PS1 mice compared to non\u2010transgenic despite equal AAV transduction efficiency between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This model has advantages over prior approaches with widespread uniform human tau expression throughout the brain and the ability to specify the stage of amyloidosis when the tau pathology is initiated. These data add further support to the amyloid cascade hypothesis and suggest RNA metabolism as a potential mechanism for amyloid\u2010induced tauopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12470","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:01:10Z","timestamp":1714449670000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Induction of tauopathy in a mouse model of amyloidosis using intravenous administration of adeno\u2010associated virus vectors expressing human P301L tau"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-9432","authenticated-orcid":false,"given":"Dylan J.","family":"Finneran","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience and the Alzheimer's Alliance Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Desjarlais","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and the Alzheimer's Alliance Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alayna","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and the Alzheimer's Alliance Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna M.","family":"Jackman","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and the Alzheimer's Alliance Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4051-9283","authenticated-orcid":false,"given":"Marcia N.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and the Alzheimer's Alliance Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and the Alzheimer's Alliance Michigan State University  Grand Rapids Michigan 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