In vivo reactive astrocyte imaging using [18F]SMBT-1 in tauopathy and familial Alzheimer's disease mouse models: A multi-tracer study

Abstract

Background: Reactive astrocytes play an important role in the development of Alzheimer's disease and primary tauopathies. Here, we aimed to investigate the relationships between reactive astrocytes. Microgliosis and glucose metabolism with Tau and amyloid beta pathology by using multi-tracer imaging in widely used tauopathy and familial Alzheimer's disease mouse models.

Results: Positron emission tomography imaging using [¹⁸F]PM-PBB3 (tau), [¹⁸F]florbetapir (amyloid-beta), [¹⁸F]SMBT-1 (monoamine oxidase-B), [¹⁸F]DPA-714 (translocator protein) and [¹⁸F]fluorodeoxyglucose was carried out in 3- and 7-month-old rTg4510 tau mice, 5 × FAD familial Alzheimer's disease mice and wild-type mice. Immunofluorescence staining was performed to validate the pathological distribution in the mouse brain after in vivo imaging. We found increased regional levels of [¹⁸F]PM-PBB3, [¹⁸F]SMBT-1, and [¹⁸F]DPA-714 and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice compared to age-matched wild-type mice. Increased [¹⁸F]SMBT-1 uptake was observed in the brains of 3, 7-month-old 5 × FAD mice, with elevated regional [¹⁸F]florbetapir and [¹⁸F]DPA-714 uptakes in the brains of 7-month-old 5 × FAD mice, compared to age-matched wild-type mice. Positive correlations were shown between [¹⁸F]SMBT-1 and [¹⁸F]PM-PBB3, [¹⁸F]DPA-714 and [¹⁸F]PM-PBB3 in rTg4510 mice, and between [¹⁸F]florbetapir and [¹⁸F]DPA-714 SUVRs in 5 × FAD mice.

Conclusion: In summary, these findings provide in vivo evidence that reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism are associated with tau and amyloid pathology development in animal models of tauopathy and familial Alzheimer's disease.

Keywords: Alzheimer's disease; Amyloid-beta; Astrocytes; Glucose metabolism; Microglia; PET; Tau.