Fig. 3

Representative [¹⁸F]THK5317 and [¹⁸F]AV1451 images of amyloid-β-negative patients with clinical diagnoses of corticobasal syndrome, progressive supranuclear palsy (PSP) syndrome, and a semantic variant of primary progressive aphasia (svPPA) (upper portion of the figure), and a tree diagram (mid portion of the figure) illustrating the poor correlation between the clinical diagnoses of corticobasal syndrome, PSP syndrome, and svPPA with pathological confirmation of the presence of tau [black font; corticobasal degeneration (CBD), PSP, Pick’s disease, Alzheimer’s disease (AD)], and TDP-43 (orange font) pathologies. The areas with high-tracer uptake are indicated with circles. The thickness of the strings (OR lines) in the diagram illustrates the approximate strength of the clinicopathological correlations [156, 237]. The lower portion of the figure shows the neuropathological and biochemical characteristics of tau pathology seen across a number of tauopathies, as well as some typical neuropathological characteristics of TDP-43 pathology. Of note, different patients were scanned for each tau PET tracer, although one can observe apparent similarities in the regional distribution of tracer uptake for [¹⁸F]THK5317 and [¹⁸F]AV1451 in the patients with the same clinical diagnosis. The patients with a clinical diagnosis of corticobasal and PSP syndromes show high binding of both tracers in relevant areas, in agreement with the expected regional distribution of CBD and PSP pathologies, respectively. Interestingly, high binding with both tracers is observed even in patients with a clinical diagnosis of svPPA, a syndrome which is not primarily associated with the presence of tau, but rather TDP-43 pathology. For the creation of parametric images for all tracers, areas of the cerebellar cortex were used as reference. The [¹⁸F]THK5317 images derive from studies performed at Karolinska Institutet, Center for Alzheimer Research [35]. The [¹⁸F]AV1451 images of the patient with corticobasal syndrome is courtesy of Chul Hyoung Lyoo (Yonsei University College of Medicine, Seoul, South Korea) [80], while the [¹⁸F]AV1451 images of the patients with PSP syndrome and svPPA are courtesy of Simon P. Jones and James Rowe (University of Cambridge, Cambridge, UK) [82, 138]. Different scales were used to better illustrate the regional distribution pattern of binding for each tracer, due to between-patient differences as well as due to the different PET acquisition parameters and quantification that were applied for each tracer or even within the same tracer between different laboratories for [¹⁸F]AV1451. BG basal ganglia, DN dentate nucleus, DVR distribution volume ratio, MB midbrain, PMC primary motor cortex, SUVR standardized uptake value ratio, TL temporal lobe, TP temporal pole, TCX temporal cortex, WM white matter