PurposeThe aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [18F]THK5317 (also known as (S)-[18F]THK5117) retention in different stages of Alzheimer’s disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.MethodsThirty-three individuals were enrolled, including nine patients with Alzheimer’s disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer’s disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [18F]THK5317, [11C] Pittsburgh compound B ([11C]PIB), and [18F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [11C]PIB-positive (n = 11) and MCI [11C]PIB-negative (n = 2) groups.ResultsTest-retest variability for [18F]THK5317-PET was very low (1.17–3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [11C]PIB-positive) and dementia-stage Alzheimer’s disease had significantly higher [18F]THK5317 retention than healthy controls (p = 0.002 and p = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [18F]THK5317 retention and [18F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [18F]THK5317 and [11C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [11C]PIB but high [18F]THK5317 retentions with a different regional distribution from that in Alzheimer’s disease patients.ConclusionsThe tau-specific PET tracer [18F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.