Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction, and Spatial Memory Deficits Reminiscent of Early Alzheimer's Disease

Neuron. 2017 Feb 8;93(3):533-541.e5. doi: 10.1016/j.neuron.2016.12.023. Epub 2017 Jan 19.


The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion when navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation system. Here we show in a transgenic mouse model expressing mutant human tau predominantly in the EC that the formation of mature tangles in old mice was associated with excitatory cell loss and deficits in grid cell function, including destabilized grid fields and reduced firing rates, as well as altered network activity. Overt tau pathology in the aged mice was accompanied by spatial memory deficits. Therefore, tau pathology initiated in the entorhinal cortex could lead to deficits in grid cell firing and underlie the deterioration of spatial cognition seen in human AD.

Keywords: Alzheimer’s disease; cognitive deficits; electrophysiology; entorhinal cortex; grid cells; hypoactivity; neurofibrillary tangles; neuronal loss; spatial memory; tau pathology.

MeSH terms

  • Action Potentials
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Animals
  • Behavior, Animal*
  • Disease Models, Animal
  • Entorhinal Cortex / pathology*
  • Entorhinal Cortex / physiopathology
  • Grid Cells / pathology*
  • Humans
  • Interneurons
  • Mice
  • Mice, Transgenic
  • Neurons / pathology
  • Spatial Memory*
  • Tauopathies
  • tau Proteins / genetics*
  • tau Proteins / metabolism


  • MAPT protein, human
  • tau Proteins