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

Abstract

Objectives: To assess [¹⁸F]AV-1451 tau-PET 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 to differentiate the PPA variants.

Methods: We 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, PiB-negative controls, age and gender matched 2:1. Principal component analysis of regional [¹⁸F]AV-1451 tau-PET SUVR 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.

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 [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 grey 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. This article is protected by copyright. All rights reserved.

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