Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease

Rik Ossenkoppele, Daniel R. Schonhaut, Michael Schoell, Samuel N. Lockhart, Nagehan Ayakta, Suzanne L. Baker, James P. O'Neil, Mustafa Janabi, Andreas Lazaris, Averill Cantwell, Jacob Vogel, Miguel Santos, Zachary A. Miller, Brianne M. Bettcher, Keith A. Vossel, Joel H. Kramer, Maria L. Gorno-Tempini, Bruce L. Miller, William J. Jagust, Gil D. Rabinovici

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The advent of the positron emission tomography tracer 18 F-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer’s disease, in contrast to the more diffuse distribution of amyloid-β pathology. We included 20 patients meeting criteria for probable Alzheimer’s disease dementia or mild cognitive impairment due to Alzheimer’s disease, presenting with a variety of clinical phenotypes, and 15 amyloid-β-negative cognitively normal individuals, who underwent 18 F-AV1451 (tau), 11 C-PiB (amyloid-β) and 18 F-FDG (glucose metabolism) positron emission tomography, apolipoprotein E ( APOE ) genotyping and neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed that 18 F-AV1451 and 18 F-FDG patterns in patients with posterior cortical atrophy (‘visual variant of Alzheimer’s disease’, n = 7) specifically targeted the clinically affected posterior brain regions, while 11 C-PiB bound diffusely throughout the neocortex. Patients with an amnestic-predominant presentation ( n = 5) showed highest 18 F-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia (‘language variant of Alzheimer’s disease’, n = 5) demonstrated asymmetric left greater than right hemisphere 18 F-AV1451 uptake in three of five patients. Across 30 FreeSurfer-defined regions of interest in 16 Alzheimer’s disease patients with all three positron emission tomography scans available, there was a strong negative association between 18 F-AV1451 and 18 F-FDG uptake (Pearson’s r = −0.49 ± 0.07, P < 0.001) and less pronounced positive associations between 11 C-PiB and 18 F-FDG (Pearson’s r = 0.16 ± 0.09, P < 0.001) and 18 F-AV1451 and 11 C-PiB (Pearson’s r = 0.18 ± 0.09, P < 0.001). Voxel-wise linear regressions thresholded at P < 0.05 (uncorrected) showed that, across all patients, younger age was associated with greater 18 F-AV1451 uptake in wide regions of the neocortex, while older age was associated with increased 18 F-AV1451 in the medial temporal lobe. APOE ϵ4 carriers showed greater temporal and parietal 18 F-AV1451 uptake than non-carriers. Finally, worse performance on domain-specific neuropsychological tests was associated with greater 18 F-AV1451 uptake in key regions implicated in memory (medial temporal lobes), visuospatial function (occipital, right temporoparietal cortex) and language (left > right temporoparietal cortex). In conclusion, tau imaging—contrary to amyloid-β imaging—shows a strong regional association with clinical and anatomical heterogeneity in Alzheimer’s disease. Although preliminary, these results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer’s disease.
Original languageEnglish
Pages (from-to)1551-1567
Publication statusPublished - 1 May 2016


  • APOE
  • AV1451 PET
  • Alzheimer's disease
  • cognition
  • tau

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