{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:07:49Z","timestamp":1789625269875,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Tau phosphorylation at T217 is a promising Alzheimer's disease (AD) biomarker, but its functional consequences were unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, tau<jats:sub>pT217<\/jats:sub>, tau<jats:sub>pT181<\/jats:sub>, tau<jats:sub>pT231<\/jats:sub>, and tau<jats:sub>pS396\/pS404<\/jats:sub>. Direct stochastic optical reconstruction microscopy (dSTORM) super resolution microscopy was used to localize tau<jats:sub>pT217<\/jats:sub> in cultured neurons. Enhanced green fluorescent protein (EGFP)\u2010tau was expressed in fibroblasts as wild type and T217E pseudo\u2010phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the brain, tau<jats:sub>pT217<\/jats:sub> appears in neurons at Braak stages I and II, becomes more prevalent later, and co\u2010localizes partially with other phospho\u2010tau epitopes. In cultured neurons, tau<jats:sub>pT217<\/jats:sub> is increased by extracellular tau oligomers (xcTauOs) and is associated with developing post\u2010synaptic sites. FRAP recovery was fastest for EGFP\u2010tau<jats:sub>T217E<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tau<jats:sub>pT217<\/jats:sub> increases in the brain as AD progresses and is induced by xcTauOs. Post\u2010synaptic tau<jats:sub>pT217<\/jats:sub> suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau's affinity for microtubules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list>\n<jats:list-item><jats:p>Validation of anti\u2010tau phosphorylated at threonine\u2010217 (tau<jats:sub>pT217<\/jats:sub>) specificity is essential due to epitope redundancy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>tau<jats:sub>pT217<\/jats:sub> increases as Alzheimer's disease progresses and is found throughout diseased neurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>tau<jats:sub>pT217<\/jats:sub> is associated with developing post\u2010synaptic sites in cultured neurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Extracellular oligomers of tau, but not amyloid beta, increase intracellular tau<jats:sub>pT217<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>T217E pseudo\u2010phosphorylation reduces tau's affinity for microtubules.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12892","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T07:01:21Z","timestamp":1673506881000},"page":"2874-2887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Localization, induction, and cellular effects of tau phosphorylated at threonine 217<sup>1<\/sup>"],"prefix":"10.1002","volume":"19","author":[{"given":"Binita","family":"Rajbanshi","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Biology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Guruacharya","sequence":"additional","affiliation":[{"name":"Instructor Group Software Carpentry  Charlottesville Virginia 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