PMC5209394_01
PET retention and neuropathology. a SUVR PET image of AV-1451. b SUVR PET image of FDG. c Transversal and lateral view z-score images of AV-1451 PET signal. d Transversal and lateral view z-score of atrophy maps based on inverted voxel-based morphometry. For both z-score images, pixels with values >1.5 (vs controls) are shown. AT8-immunohistochemistry at x10 (upper panel) or x20 (lower panel) magnification of frontal pole cortex (e, f), occipital cortex (g, h), dorsal midbrain (i, j), substantia nigra (k, l), globus pallidus (m, n), and cerebellar cortex (o, p). Scale bars 50 microm. q
18F-AV-1451 SUVRs plotted against the tau-positive neurite density. An annotated version of this figure is available as Supplementary Fig. 2. r
18F-FDG SUVRs plotted against neurite density
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Fig1
Supplementary material for detail). Seven months prior to death the subject was scanned with 18F-AV-1451 PET, 18F-AV-FDG-PET, and MRI (Fig. 1a-d). 18F-AV-1451 PET showed retention in the basal ganglia, but not cortex (Fig. 1a, c). 18F-AV-FDG-PET revealed decreased metabolism in the frontal cortex and basal ganglia (Fig. 1b). Voxel-based morphometry showed cortical atrophy, predominantly in the frontal cortex (Fig. 1d). Tau-positive (AT8 immunohistochemistry) neurites and cell bodies were quantified using unbiased stereology (see supplement and  for methods), and results were correlated with 18F-AV-1451 and 18F-FDG retention in the same regions (Fig. 1 ). In the frontal, temporal, and parietal cortex and subcortical white matter, there was widespread tau pathology, whereas the occipital lobe and cerebellar grey matter were relatively spared (Fig. 1e-p). Comparing the 18F-AV-1451 retention to neurite density, there was no correlation between PET signal and the intensity of the pathology (r s = 0.23; p = 0.29; Fig. 1q). Furthermore, autoradiography of AV-1451 and THK-5351 showed no specific binding to tau pathology (Supplementary Fig. 1). 18F-FDG retention in the cerebral cortex, brain stem, and basal ganglia showed a clear inverse correlation to tau neuropathology (r s = -0.78; p = 0.01; Fig. 1r). 