ObjectivesTo assess [¹⁸F]AV‐1451 tau‐PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [¹⁸F]AV‐1451 independent of clinical diagnosis, and compare the diagnostic utility of [¹⁸F]AV‐1451, [¹⁸F]‐fluorodeoxygluclose (FDG)‐PET and MRI (magnetic resonance imaging) to differentiate the PPA variants.MethodsWe performed statistical parametric mapping of [¹⁸F]AV‐1451 across 40 PPA patients (logopenic‐PPA = 14, semantic‐PPA = 13, and agrammatic‐PPA = 13) compared to 80 cognitively normal, Pittsburgh compound B–negative controls, age and gender matched 2:1. Principal component analysis of regional [¹⁸F]AV‐1451 tau‐PET standard uptake value ratio was performed to understand underlying patterns of [¹⁸F]AV‐1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility.ResultsLogopenic‐PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic‐PPA, and agrammatic‐PPA. Semantic‐PPA and agrammatic‐PPA showed milder patterns of focal [¹⁸F]AV‐1451 uptake. Semantic‐PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic‐PPA. Agrammatic‐PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic‐PPA. The principal component analysis of regional [¹⁸F]AV‐1451 indicated two primary dimensions, a severity dimension that distinguished logopenic‐PPA from agrammatic‐PPA and semantic‐PPA, and a frontal versus temporal contrast that distinguishes agrammatic‐PPA and semantic‐PPA cases. Diagnostic utility of [¹⁸F]AV‐1451was superior to MRI and at least equal to FDG‐PET.Interpretation[¹⁸F]AV‐1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [¹⁸F]AV‐1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [¹⁸F]AV‐1451 may have clinical diagnostic utility in PPA. Ann Neurol 2018 Ann Neurol 2018;83:599–611