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However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217\/T217) and amyloid\u2010beta (A\u03b2) 42\/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Individuals with AD had high CSF pT217\/T217 and low A\u03b242\/40. In contrast, cognitively normal individuals and the majority of those with 4R tauopathies had low CSF pT217\/T217 and normal A\u03b2 42\/40. We identified a subgroup of individuals with increased CSF pT217\/T217 and normal A\u03b2 42\/40 ratio, most of whom were <jats:italic>MAPT<\/jats:italic> R406W mutation carriers. Diagnostic accuracies of CSF A\u03b2 42\/40 and CSF pT217\/T217, alone and in combination were compared. We show that CSF pT217\/T217\u00a0\u00d7\u00a0CSF A\u03b2 42\/40 is a sensitive composite biomarker that can separate <jats:italic>MAPT<\/jats:italic> R406W carriers from cognitively normal individuals and those with other tauopathies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p><jats:italic>MAPT<\/jats:italic> R406W is a tau mutation that leads to 3R+4R tauopathy similar to AD, but without amyloid neuropathology. These findings suggest that change in CSF pT217\/T217 ratio is not specific to AD and might reflect common downstream tau pathophysiology common to 3R+4R tauopathies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51435","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T06:42:55Z","timestamp":1627972975000},"page":"1817-1830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<i>MAPT<\/i> R406W increases tau T217 phosphorylation in absence of amyloid pathology"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7639-8727","authenticated-orcid":false,"given":"Chihiro","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University School of Medicine St. Louis 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