[¹⁸ F]AV-1451 tau-PET and primary progressive aphasia

Objectives: To assess [¹⁸ F]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 [¹⁸ F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [¹⁸ F]AV-1451, [¹⁸ F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging) to differentiate the PPA variants.

Methods: We performed statistical parametric mapping of [¹⁸ F]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 [¹⁸ F]AV-1451 tau-PET standard uptake value ratio was performed to understand underlying patterns of [¹⁸ F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility.

Results: Logopenic-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 [¹⁸ F]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 [¹⁸ F]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 [¹⁸ F]AV-1451was superior to MRI and at least equal to FDG-PET.

Interpretation: [¹⁸ F]AV-1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [¹⁸ F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [¹⁸ F]AV-1451 may have clinical diagnostic utility in PPA. Ann Neurol 2018 Ann Neurol 2018;83:599-611.