Abstract

[18F]AV-1451 is a PET tracer in development for assessment of neurofibrillary tau pathology. As tau pathology is likely a biomarker of neurodegeneration, characterizing the rate of change in the tau signal in Alzheimer’s Disease (AD) should be useful to follow disease progression. Subjects clinically diagnosed as healthy controls (HC), Mild Cognitive Impairment (MCI) or AD were enrolled for [18F]AV-1451PET imaging (∼370 MBq iv; scanning 80-100 min post injection) at baseline, 9 months and 18 months. Images were co-registered and resampled into MNI atlas space. Activity in atlas-based ROIs as well as a large average ROI were normalized by cerebellar gray matter to create regional SUV ratio (SUVr). Amyloid imaging (∼370 MBq i.v. florbetapir) was done at baseline and reviewed using standard methods to determine amyloid positivity (Aβ+). Scan data is available on n=217 at baseline, n=164 at 9 months but presently only n=34 at 18 months. Interim analysis of the 9 month data showed the Aβ+ group (n=65: 24 AD, 36 MCI and 5 HC) had a significant [18F]AV-1451 SUVr increase in the large cortical ROI (paired t-test p=0.0002; mean ± S.D 1.50±0.39 at baseline and 1.54±0.44 at 9 mos; Δ=0.039±0.079). No significant change (p=0.6) was seen in the Aβ- subjects. For Aβ+ subjects, ROIs with largest SUVr increases included parietal (Δ=0.030±0.066) and posterior fusiform (Δ=0.032±0.077), while the smallest change was seen in anterior mesial temporal lobe regions (e.g., anterior parahippocampal Δ=0.007±0.069). SUVr change for many regions was inversely correlated to age and positively correlated to baseline tau signal (large cortical ROI r = -0.43 and r=+0.53, respectively). [18F]AV-1451 PET tau signal in Aβ+ subjects increased significantly over 9 months across multiple brain regions, consistent with ongoing neurodegeneration. The observations that the change in SUVr correlates to both age and to baseline SUVr is preliminary, but could indicate differences in aggressiveness and underlying stage of the disease. The 18 month scan visits should be complete in 2Q 2016 and will allow additional measures of the [18F]AV-1451 PET tau signal change over time as well as comparison of tau signal changes to changes in cognitive measures.

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