Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies

Acta Neuropathol. 2015 Nov;130(5):619-31. doi: 10.1007/s00401-015-1483-3. Epub 2015 Oct 6.


Pathological tau aggregation leads to filamentous tau inclusions and characterizes neurodegenerative tauopathies such as Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregation coincides with clinical symptoms and is thought to mediate neurodegeneration. Transgenic mice overexpressing mutant human P301S tau exhibit many neuropathological features of human tauopathies including behavioral deficits and increased mortality. Here, we show that the di-phenyl-pyrazole anle138b binds to aggregated tau and inhibits tau aggregation in vitro and in vivo. Furthermore, anle138b treatment effectively ameliorates disease symptoms, increases survival time and improves cognition of tau transgenic PS19 mice. In addition, we found decreased synapse and neuron loss accompanied by a decreased gliosis in the hippocampus. Our results suggest that reducing tau aggregates with anle138b may represent an effective and promising approach for the treatment of human tauopathies.

Keywords: Alzheimer’s disease; Anle138b; Protein aggregation; Tau; Tau aggregation inhibitor; Tauopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodioxoles / pharmacology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gliosis / drug therapy
  • Gliosis / pathology
  • Gliosis / physiopathology
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Male
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Protein Aggregates / drug effects
  • Pyrazoles / pharmacology*
  • Random Allocation
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology
  • Tauopathies / drug therapy*
  • Tauopathies / pathology
  • tau Proteins / genetics
  • tau Proteins / metabolism*


  • 3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole
  • Benzodioxoles
  • MAPT protein, human
  • Mapt protein, mouse
  • Neuroprotective Agents
  • Protein Aggregates
  • Pyrazoles
  • tau Proteins