In vivo [18F]SMBT‐1 imaging of reactive astrocytes in mouse models of Alzheimer’s disease ‐ temporospatial relationship with amyloid, tau and microgliosis

Abstract

AbstractBackgroundReactive astrocytes play an important role in the pathogenesis of Alzheimer’s disease (AD). Here, we aim to investigate the temporospatial relationship between reactive astrocytes, microgliosis, tau and amyloid‐β by using in vivo multitracer imaging in AD transgenic mouse models.MethodPositron emission tomography (PET) imaging with [18F]SMBT‐1 (monoamine oxidase‐B for reactive astrocytes), [18F]DPA‐14 (translocator protein for microgliosis), [18F]PBB3 (tau), and [18F]florbetapir (Aβ) was carried out in 5‐ and 12‐month‐old APP/PS1, 12‐month‐old 3×Tg mice, and aged‐matched wild‐type mice. The brain regional referenced standard uptake value (SUVR) was computed with the cerebellum as reference region. Immunofluorescence staining was performed with antibodies against monoamine oxidase‐B, astrocytes, translocator protein, microglia, tau, and amyloid in mouse brain slices.Result[18F]SMBT‐1 SUVRs were higher in the cortex and hippocampus of 12‐month‐old APP/PS1 mice than age‐matched wild‐type mice. [18F]DPA‐14 SUVRs were higher in the brain stem and amygdala of 5 and 12‐month‐old APP/PS1 mice than in age‐matched wild‐type mice. [18F]PBB3 were higher in the cortex, striatum and hippocampus of APP/PS1 mice than in 5‐month‐old APP/PS1 mice and wild‐type mice. [18F]florbetapir SUVRs were higher in the brain stem, thalamus and midbrain of APP/PS1 mice at 5 months than in age‐matched wild‐type mice. No significant difference in the regional [18F]SMBT‐1, [18F]DPA‐14, [18F]PBB3, [18F]florbetapir or [11C]PIB SUVR was observed in 12‐month‐old 3×Tg mice compared to age‐matched wild‐type mice, which is validated by the limited 6E10‐positive amyloid plaques and AT8‐positive tau deposits.ConclusionThe findings provide in vivo evidence for different regional distribution of reactive astrocytes and microgliosis in animal models of AD.