In vivo reactive astrocyte imaging using [18F]SMBT-1 in tauopathy and familial Alzheimer’s disease mouse models - a multitracer study

Abstract

Abstract Background: Reactive astrocytes play important roles in the development of Alzheimer’s disease (AD) and primary tauopathies. Here, we aim to investigate the relationship between reactive astrocytes, tau and amyloid beta, microgliosis and glucose metabolism by using multitracer imaging in widely used tauopathy and familial AD mouse models. Results: Positron emission tomography (PET) imaging using [18F]SMBT-1 (monoamine oxidase-B), [18F]florbetapir (amyloid-beta), [18F]PM-PBB3 (tau), [18F]DPA-714 (translocator protein) and [18F]fluorodeoxyglucose (FDG) was carried out in 3- and 7-month-old rTg4510 tau mice, 5×FAD familial AD mice and aged-matched wild-type mice. We found increased regional [18F]SMBT-1, [18F]DPA-714 uptake, and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice with tau accumulation as well as in 7-month-old 5×FAD mice with higher amyloid-beta and tau accumulation compared to age-matched wild-type mice. Conclusion: In summary, these findings provide in-vivo evidence for reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism in animal models of tauopathy and familial AD.