Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls

Neuron. 2013 Sep 18;79(6):1094-108. doi: 10.1016/j.neuron.2013.07.037.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Aminopyridines / pharmacokinetics
  • Amyloid beta-Peptides / metabolism
  • Aniline Compounds
  • Animals
  • Autoradiography
  • Benzothiazoles / chemistry
  • Benzothiazoles / pharmacokinetics
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / pathology*
  • Brain Mapping
  • Calcium-Binding Proteins
  • Carbon Isotopes / pharmacokinetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins
  • Middle Aged
  • Mutation / genetics
  • Positron-Emission Tomography
  • Protein Structure, Secondary
  • Tauopathies / diagnostic imaging
  • Tauopathies / pathology*
  • Thiazoles
  • tau Proteins / genetics
  • tau Proteins / metabolism*

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • 2-(6-(methylamino)pyridin-3-yl)-1,3-benzothiazol-6-ol
  • AIF1 protein, human
  • Aminopyridines
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Calcium-Binding Proteins
  • Carbon Isotopes
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Thiazoles
  • tau Proteins
  • benzothiazoline