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Using liquid chromatography\u2013tandem mass spectrometry, we compared tau modifications in\n                    <jats:italic>MAPT<\/jats:italic>\n                    knock\u2010in (\n                    <jats:italic>MAPT<\/jats:italic>\n                    KI) mice and\n                    <jats:italic>MAPT<\/jats:italic>\n                    \/\n                    <jats:italic>App<\/jats:italic>\n                    double knock\u2010in mice with\n                    <jats:italic>App<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>NL\u2010G\u2010F<\/jats:italic>\n                    <\/jats:sup>\n                    amyloid pathology. Only subtle differences were detected, with a tendency toward increased acetylation within the repeat domain. Because K321 and K331 lie in the fibril\u2010forming core, their roles were further examined. Acetylation at these sites was absent in cynomolgus monkey brains. To test functional relevance, we generated acetylation\u2010mimicking\n                    <jats:italic>MAPT<\/jats:italic>\n                    <jats:sup>K331Q<\/jats:sup>\n                    knock\u2010in mice on the\n                    <jats:italic>MAPT<\/jats:italic>\n                    KI background. Despite tau expression, these mice showed reduced tau phosphorylation at 24\u2009months, with unchanged insoluble tau and seeding activity. Thus, K331 acetylation does not promote tau pathology.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70320","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:20:53Z","timestamp":1773138053000},"page":"2050-2062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tau acetylation at\n                    <scp>K331<\/scp>\n                    has limited impact on tau pathology\n                    <i>in vivo<\/i>"],"prefix":"10.1002","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-4884","authenticated-orcid":false,"given":"Shoko","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Pioneering Research Division, Medical Innovation Research Center Shiga University of Medical Science  Otsu Shiga Japan"},{"name":"Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science  Wako Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Matsuba","sequence":"additional","affiliation":[{"name":"Pioneering Research Division, Medical Innovation Research Center Shiga University of Medical Science  Otsu Shiga Japan"},{"name":"Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science  Wako Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science  Wako Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1970-6903","authenticated-orcid":false,"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[{"name":"Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science  Wako Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1349-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0199-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4443"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0172-12.2012"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-52"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3697"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.029"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39328-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4067"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10278-x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009487"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2025.101024"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01829-7"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411649111"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2004.08.010"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.11.029"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96627-7"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2023.05.020"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.794602"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2022.2081165"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.08.044"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41672-1"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1255"}],"container-title":["FEBS 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