Abstract
Accumulation of intracellular tau fibrils has been the focus of research on the mechanisms of neurodegeneration in Alzheimer's disease (AD) and related tauopathies. Here, we have developed a class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders. In vivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection of tau inclusions by PBBs. A pyridinated PBB, [(11)C]PBB3, was next applied in a clinical PET study, and its robust signal in the AD hippocampus wherein tau pathology is enriched contrasted strikingly with that of a senile plaque radioligand, [(11)C]Pittsburgh Compound-B ([(11)C]PIB). [(11)C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [(11)C]PBB3 signals were found in a corticobasal syndrome patient negative for [(11)C]PIB-PET.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Aged
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Alzheimer Disease / diagnostic imaging
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Alzheimer Disease / pathology*
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Aminopyridines / pharmacokinetics
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Amyloid beta-Peptides / metabolism
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Aniline Compounds
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Animals
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Autoradiography
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Benzothiazoles / chemistry
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Benzothiazoles / pharmacokinetics
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Brain / diagnostic imaging
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Brain / drug effects
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Brain / pathology*
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Brain Mapping
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Calcium-Binding Proteins
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Carbon Isotopes / pharmacokinetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Female
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Humans
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Magnetic Resonance Imaging
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microfilament Proteins
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Middle Aged
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Mutation / genetics
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Positron-Emission Tomography
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Protein Structure, Secondary
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Tauopathies / diagnostic imaging
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Tauopathies / pathology*
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Thiazoles
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tau Proteins / genetics
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tau Proteins / metabolism*
Substances
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2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
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2-(6-(methylamino)pyridin-3-yl)-1,3-benzothiazol-6-ol
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AIF1 protein, human
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Aminopyridines
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Amyloid beta-Peptides
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Aniline Compounds
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Benzothiazoles
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Calcium-Binding Proteins
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Carbon Isotopes
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DNA-Binding Proteins
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Microfilament Proteins
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Thiazoles
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tau Proteins
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benzothiazoline