Characterization of [18F]SMBT-1 binding substrates in Alzheimer's disease and related disorders: A postmortem biochemical and immunohistochemical study

Introduction: Neuroimaging studies report associations of amyloid beta (Aβ) positron emission tomography (PET) with [18F](S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([18F]SMBT-1), a novel reactive astrogliosis surrogate radiotracer with high affinity for monoamine oxidase B (MAO-B) in Alzheimer's disease (AD). Postmortem association of [18F]SMBT-1 binding with pathology of AD and non-AD tauopathies is undefined. Methods: [18F]SMBT-1 binding, [3H]Pittsburgh compound B ([3H]PiB) binding, and MAO-B activity assays in brain homogenates, with [18F]SMBT-1 autoradiography and MAO-B immunoreactivity in relation to glial fibrillary acidic protein (GFAP), major histocompatibility complex II (MHC-II), Aβ, phosphorylated tau, cyano-Pittsburgh compound B (cyano-PiB), and X-34 on brain sections from AD, non-AD tauopathies, and nondemented controls. Results: [18F]SMBT-1 binding correlated with MAO-B activity and [3H]PiB binding, with highest levels in AD. [18F]SMBT-1 autoradiography corresponded to MAO-B/GFAP-immunoreactive astrocytes associated with Aβ deposits in plaques and vasculature, more closely than to tau pathology. [18F]SMBT-1 binding and MAO-B activity in non-AD tauopathies partially overlapped controls and AD, with MAO-B/GFAP-immunoreactive astrocytes in areas with tau pathology. Discussion: [18F]SMBT-1 is a promising biomarker of MAO-B reactive astrocytes in AD and non-AD tauopathies.