Format

Send to

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

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

Author information

1
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
2
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: sah2149@columbia.edu.
3
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA; Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA. Electronic address: ked2115@columbia.edu.

Abstract

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

PMID:
28111080
PMCID:
PMC5363269
DOI:
10.1016/j.neuron.2016.12.023
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center