Characterization of [ 18 F]SMBT‐1 binding substrates in Alzheimer's disease and related disorders: A postmortem biochemical and immunohistochemical study
Eric E. Abrahamson, Julia K. Kofler, Oscar L. Lopez, Anne D. Cohen, Alexandra Gogola, Howard J. Aizenstein, Thomas K. Karikari, Elliott J. Mufson, Victor L. Villemange, Milos D. IkonomovicAbstract
INTRODUCTION
Neuroimaging studies report associations of amyloid beta (Aβ) positron emission tomography (PET) with [ 18 F](S)‐(2‐methylpyrid‐5‐yl)‐6‐[(3‐fluoro‐2‐hydroxy)propoxy]quinoline ([ 18 F]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 [ 18 F]SMBT‐1 binding with pathology of AD and non‐AD tauopathies is undefined.
METHODS
[ 18 F]SMBT‐1 binding, [ 3 H]Pittsburgh compound B ([ 3 H]PiB) binding, and MAO‐B activity assays in brain homogenates, with [ 18 F]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
[ 18 F]SMBT‐1 binding correlated with MAO‐B activity and [ 3 H]PiB binding, with highest levels in AD. [ 18 F]SMBT‐1 autoradiography corresponded to MAO‐B/GFAP‐immunoreactive astrocytes associated with Aβ deposits in plaques and vasculature, more closely than to tau pathology. [ 18 F]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
[ 18 F]SMBT‐1 is a promising biomarker of MAO‐B reactive astrocytes in AD and non‐AD tauopathies.