Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using C-11-BU99008 PET and its relationship with amyloid load

C-11-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer's disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), F-18-florbetaben and C-11-BU99008 PET. The 8 amyloid (A beta)-positive CI subjects had higher C-11-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between C-11-BU99008 and F-18-florbetaben. Autoradiography using H-3-BU99008 with post-mortem Alzheimer's brains confirmed through visual assessment that increased H-3-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that C-11-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer's disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high A beta load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.