EVALUATION OF TAU BURDEN IN A CROSS-SECTIONAL COHORT OF ALZHEIMER’S DISEASE SUBJECTS USING [18F]GTP1 (GENENTECH TAU PROBE 1)

Abstract

In Alzheimer’s disease (AD), the extent and density of tau pathology (intracellular aggregates of hyperphosphorylated tau) correlates with disease severity prior to death. [18F]GTP1 is a tau PET tracer that exhibits rapid pharmacokinetics, enabling the use of SUVR60-90min as a surrogate measure of tau specific binding, and robust test-retest reliability. Here, we report the preliminary results on the distribution of tau pathology, assessed by [18F]GTP1 PET imaging, and its relationship with symptomatic severity in an AD cross-sectional cohort enrolling as part of a longitudinal 18-month natural history study. Subjects were enrolled in an ongoing longitudinal natural history study; enrollment goals: 5 amyloid(-) and 5 amyloid (+) cognitively normal (MMSE 28-30, CDR 0), 20 prodromal AD (amyloid(+), MMSE 24-30, CDR = 0.5), 20 mild AD (amyloid(+), MMSE 22-30, CDR 0.5 or 1) and 10 moderate AD (amyloid(+), MMSE 16-21, CDR 1 or 2), all subjects are between the age of 50 and 80, inclusive. Clinical evaluations include MMSE, ADAS-cog-13, CDR, RBANS, and Stroop color naming. [18F]GTP1 images are being acquired over a 30-minute window starting 60 minutes post injection. The cerebellum gray has been shown to be an adequate reference region to estimate the non-displaceable component in cortical regions1, thus is being used to calculate SUVR. Consistent with observations from a first-in-human study, visual inspection of images suggest [18F]GTP1 exhibits a wide dynamic range and allows differentiation between AD and healthy controls, and between regions of predicted high and low tau pathology burden ((1)). In addition, we are investigating how global [18F]GTP uptake relates with global measures of clinical severity, and how regional distribution of [18F]GTP uptake relates to specific cognitive deficits. Interim analysis from this ongoing study will be presented. [18F]GTP1 is currently under evaluation in a longitudinal natural history study. Preliminary cross-sectional results reveal how the extent of GTP1 uptake relates to clinical cognitive and functional deficits in AD.