A study using the PET tracer 18F-AV1451 reveals that tau pathology in Alzheimer's disease (AD) closely mirrors clinical and neuroanatomical variability, unlike the diffuse distribution of amyloid-β pathology. The study included 20 patients with probable AD dementia or mild cognitive impairment due to AD, and 15 amyloid-β-negative cognitively normal individuals, all undergoing 18F-AV1451 (tau), 11C-PiB (amyloid-β), and 18F-FDG (glucose metabolism) PET scans, along with neuropsychological testing and APOE genotyping. Voxel-wise contrasts showed that 18F-AV1451 patterns in patients with posterior cortical atrophy (PCA) specifically targeted clinically affected posterior brain regions, while 11C-PiB was diffuse throughout the neocortex. Patients with amnestic-predominant presentations showed highest 18F-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia (PPA) demonstrated asymmetric left greater than right hemisphere 18F-AV1451 uptake. Across 30 FreeSurfer-defined regions, there was a strong negative association between 18F-AV1451 and 18F-FDG uptake, and less pronounced positive associations between 11C-PiB and 18F-FDG, and between 18F-AV1451 and 11C-PiB. Younger age was associated with greater 18F-AV1451 uptake in wide neocortical regions, while older age was associated with increased 18F-AV1451 in the medial temporal lobe. APOE ε4 carriers showed greater temporal and parietal 18F-AV1451 uptake than non-carriers. Worse performance on domain-specific neuropsychological tests was associated with greater 18F-AV1451 uptake in key regions implicated in memory, visuospatial function, and language. The study concludes that tau imaging shows a strong regional association with clinical and anatomical heterogeneity in AD, consistent with findings from post-mortem, animal, and CSF studies, suggesting that tau pathology is closely linked to neurodegeneration and clinical manifestations of AD.A study using the PET tracer 18F-AV1451 reveals that tau pathology in Alzheimer's disease (AD) closely mirrors clinical and neuroanatomical variability, unlike the diffuse distribution of amyloid-β pathology. The study included 20 patients with probable AD dementia or mild cognitive impairment due to AD, and 15 amyloid-β-negative cognitively normal individuals, all undergoing 18F-AV1451 (tau), 11C-PiB (amyloid-β), and 18F-FDG (glucose metabolism) PET scans, along with neuropsychological testing and APOE genotyping. Voxel-wise contrasts showed that 18F-AV1451 patterns in patients with posterior cortical atrophy (PCA) specifically targeted clinically affected posterior brain regions, while 11C-PiB was diffuse throughout the neocortex. Patients with amnestic-predominant presentations showed highest 18F-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia (PPA) demonstrated asymmetric left greater than right hemisphere 18F-AV1451 uptake. Across 30 FreeSurfer-defined regions, there was a strong negative association between 18F-AV1451 and 18F-FDG uptake, and less pronounced positive associations between 11C-PiB and 18F-FDG, and between 18F-AV1451 and 11C-PiB. Younger age was associated with greater 18F-AV1451 uptake in wide neocortical regions, while older age was associated with increased 18F-AV1451 in the medial temporal lobe. APOE ε4 carriers showed greater temporal and parietal 18F-AV1451 uptake than non-carriers. Worse performance on domain-specific neuropsychological tests was associated with greater 18F-AV1451 uptake in key regions implicated in memory, visuospatial function, and language. The study concludes that tau imaging shows a strong regional association with clinical and anatomical heterogeneity in AD, consistent with findings from post-mortem, animal, and CSF studies, suggesting that tau pathology is closely linked to neurodegeneration and clinical manifestations of AD.