Relationship between reactive astrocytes, by SMBT-1 imaging, with amyloid-beta, tau, glucose metabolism, and microgliosis in mouse models of Alzheimer's disease

Kong, Y.; Maschio, C.; Shi, X.; Yao, B.; Xie, F.; Zuo, C.; Konietzko, U.; Shi, K.; Rominger, A.; Xiao, J.; Huang, Q.; Nitsch, R. M.; Guan, Y.; Ni, R.

doi:10.1101/2023.08.21.554163

bioRxiv · 10.1101/2023.08.21.554163

Relationship between reactive astrocytes, by SMBT-1 imaging, with amyloid-beta, tau, glucose metabolism, and microgliosis in mouse models of Alzheimer's disease

Kong, Y.·Maschio, C.·Shi, X.·Yao, B.·Xie, F.·Zuo, C.·Konietzko, U.·Shi, K.·Rominger, A.·Xiao, J.·Huang, Q.·Nitsch, R. M.·Guan, Y.·Ni, R.

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Abstract

PurposeReactive astrocytes play an important role in the development of Alzheimers disease (AD). Here, we aim to investigate the temporospatial relationship between reactive astrocytes, tau and amyloid-{beta}, glucose metabolism, and microgliosis by using multitracer imaging in AD transgenic mouse models. MethodsPositron emission tomography (PET) imaging with [18F]SMBT-1 (monoamine oxidase-B), [18F]florbetapir (A{beta}), [18F]PM-PBB3 (tau), [18F]FDG, and [18F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3xTg mice, and aged-matched wild-type mice. The brain regional referenced standard uptake value (SUVR) was computed with the cerebellum as the reference region. Immunofluorescence staining was performed in mouse brain tissue slices. Results[18F]SMBT-1 and [18F]florbetapir SUVRs were higher in the cortex and hippocampus of 10-month-old APP/PS1 mice than in 5-month-old APP/PS1 mice and wild-type mice. Reduced [18F]FDG SUVR was observed in the thalamus and midbrain of 5-month-old APP/PS1 mice compared to wild-type mice. No significant difference in brain regional [18F]DPA-714 SUVR was observed in 5- and 10-month-old APP/PS1 mice compared to wild- type mice. No significant difference in the SUVRs of any tracers was observed in 11-month-old 3xTg mice compared to age-matched wild-type mice. A positive correlation between the SUVRs of [18F]SMBT-1 and [18F]DPA-714 in the cortex was observed. Immunostaining validated the distribution of MAO-B and TSPO, amyloid and tau inclusions in brain tissue from 10-month-old APP/PS1 mice and limited changes in 11-month- old 3xTg mice. ConclusionThe findings provide in vivo evidence for reactive astrocytes along with amyloid plaque and tau deposition preceding microgliosis in animal models of AD pathologies.

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Kong, Y., Maschio, C., Shi, X., Yao, B., Xie, F., Zuo, C., Konietzko, U., Shi, K., Rominger, A., Xiao, J., Huang, Q., Nitsch, R. M., Guan, Y., Ni, R.. 2023-08-22. Relationship between reactive astrocytes, by SMBT-1 imaging, with amyloid-beta, tau, glucose metabolism, and microgliosis in mouse models of Alzheimer's disease. https://doi.org/10.1101/2023.08.21.554163

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