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

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.

journal_name

Neuron

journal_title

Neuron

authors

Fu H,Rodriguez GA,Herman M,Emrani S,Nahmani E,Barrett G,Figueroa HY,Goldberg E,Hussaini SA,Duff KE

doi

10.1016/j.neuron.2016.12.023

subject

Has Abstract

pub_date

2017-02-08 00:00:00

pages

533-541.e5

issue

3

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(16)30996-5

journal_volume

93

pub_type

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