{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:51:28Z","timestamp":1791337888348,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000135","name":"NIH Blueprint for Neuroscience Research","doi-asserted-by":"publisher","award":["AG061892"],"award-info":[{"award-number":["AG061892"]}],"id":[{"id":"10.13039\/100000135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000135","name":"NIH Blueprint for Neuroscience Research","doi-asserted-by":"publisher","award":["AG055798"],"award-info":[{"award-number":["AG055798"]}],"id":[{"id":"10.13039\/100000135","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":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To illuminate the pathological synergy between A\u03b2 and tau leading to emergence of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), here, we have performed a comparative neuropathological study utilising three distinctive variants of human tau (WT tau, P301L mutant tau and S320F mutant tau). Previously, in non\u2010transgenic mice, we showed that WT tau or P301L tau does not form NFT while S320F tau can spontaneously aggregate into NFT, allowing us to test the selective vulnerability of these different tau conformations to the presence of A\u03b2 plaques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We injected recombinant AAV\u2010tau constructs into neonatal\n                      <jats:italic>APP<\/jats:italic>\n                      transgenic TgCRND8 mice or into 3\u2010month\u2010old TgCRND8 mice; both cohorts were aged 3\u00a0months post injection. This allowed us to test how different tau variants synergise with soluble forms of A\u03b2 (pre\u2010deposit cohort) or with frank A\u03b2 deposits (post\u2010deposit cohort).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Expression of WT tau did not produce NFT or altered A\u03b2 in either cohort. In the pre\u2010deposit cohort, S320F tau induced A\u03b2 plaque deposition, neuroinflammation and synaptic abnormalities, suggesting that early tau tangles affect the amyloid cascade. In the post\u2010deposit cohort, contemporaneous expression of S320F tau did not exacerbate amyloid pathology, showing a dichotomy in A\u03b2\u2010tau synergy based on the nature of A\u03b2. P301L tau produced NFT\u2010type inclusions in the post\u2010deposit cohort, but not in the pre\u2010deposit cohort, indicating pathological synergy with pre\u2010existing A\u03b2 deposits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data show that different tau mutations representing specific folding variants of tau synergise with A\u03b2 to different extents, depending on the presence of cerebral deposits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12779","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:53:12Z","timestamp":1637887992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Combinatorial model of amyloid \u03b2 and tau reveals synergy between amyloid deposits and tangle formation"],"prefix":"10.1111","volume":"48","author":[{"given":"Emily J.","family":"Koller","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Florida  Gainesville Florida USA"},{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville Florida USA"},{"name":"Department of Neuroscience Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen R.","family":"Ibanez","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Vo","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Neurodegenerative Disease University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen 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