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Distinct [18F]AV1451 retention patterns in clinical variants of Alzheimer’s disease

      Background

      To describe preliminary findings applying the putative tau PET ligand [18F]AV1451 (formerly named T807) in clinical variants of Alzheimer’s disease (AD) and to compare the regional specificity of [18F]AV1451 to that of [11C]PIB (measure of amyloid pathology) and [18F]FDG (glucose metabolism) PET.

      Methods

      PET scans were performed in 5 posterior cortical atrophy (PCA), 4 logopenic variant primary progressive aphasia (lvPPA), 1 early-onset AD and 2 (memory-predominant) late-onset AD patients (all PIB+) and in 19 cognitively normal controls (Table 1). We created SUVr images for [18F]AV1451 (80-100 minutes, gray matter cerebellum as reference region) and [18F]FDG (30-60 minutes, pons-normalized), and DVR images for [11C]PIB (0-90 minutes, gray matter cerebellum as reference region). We visually assessed [18F]AV1451, [11C]PIB and [18F]FDG uptake patterns in 3 distinct AD variants, and performed voxel-wise contrasts (in SPM) between PCA patients and controls.

      Results

      Figure 1 shows asymmetric [18F]AV1451 uptake in parietal, temporal and frontal regions (left>right) in a patient with lvPPA, a classical temporoparietal pattern in a patient with memory-predominant AD, and mainly occipitotemporal and occipitoparietal involvement in a PCA patient. [18F]AV1451 and [18F]FDG appeared strikingly as mirror images, with regions of high [18F]AV1451 uptake corresponding to low [18F]FDG uptake and vice versa, while [11C]PIB binding was observed throughout the association neocortex. Voxelwise contrasts with [18F]AV1451 and [18F]FDG showed that PCA patients significantly differed from controls in clinically affected posterior brain regions, while [11C]PIB binding was greater in both posterior regions and in clinically less affected anterior regions (Figure 2).

      Conclusions

      [18F]AV1451 was specifically retained in brain regions closely related to the clinical presentation across distinct AD variants and overlapped substantially with hypometabolic regions in PCA, while [11C]PIB binding was more diffuse and showed less overlap with [18F]FDG uptake. This provides preliminary in-vivo evidence that hypometabolism and symptomatology are more closely linked to tau than to Aβ pathology.
      Table 1Demographics and regional PET uptake
      PCAlyPPAEOAD/LOADControls
      N54319
      Age64636879
      Sex (m/f)2/31/30/36/13
      MMSE23202229
      [18F]AV1451 SUYr (Tau)
      Occipital2.211.711.651.06
      Parietal2.412.262.201.11
      Temporal2.042.362.121.15
      Frontal1.561.791.361.10
      MTL1.471.301.671.18
      [18E]FDG SUYc (Glucose metabolism)
      Occipital1.311.891.781.59
      Parietal1.181.431.411.55
      Temporal1.131.251.241.35
      Frontal1.431.531.581.50
      MTL1.031.111.091.11
      [11C]PIB DVR (Amyloid)
      Occipital1.491.651.381.09
      Parietal1.802.171.841.19
      Temporal1.612.021.631.08
      Frontal1.792.281.821.13
      MTL1.121.341.211.05
      Data are presented as mean values (except for sex).
      PCA = Posterior cortical atrophy; = logppenic variant primary progressive aphasia; EOAD = early-onset Alzheimer's disease; LOAD = late-onset Alzheimer’s disease; SUVr = Standardized uptake value ratio; DVR = Distribution volume ratio.
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