title: 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.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Fu
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Rodriguez
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Herman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Sheina
authors.initials: S
authors.lastname: Emrani
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Eden
authors.initials: E
authors.lastname: Nahmani
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Barrett
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Figueroa
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Goldberg
authors.affiliation: 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.
authors.forename: S Abid
authors.initials: SA
authors.lastname: Hussaini
authors.affiliation: 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.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Duff
mesh_terms: D000200:Action Potentials; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000473:pathology* / Q000503:physiopathology; D000071038:Grid Cells / Q000473:pathology*; D006801:Humans; D007395:Interneurons; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D065852:Spatial Memory; D024801:Tauopathies; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer’s disease; cognitive deficits; electrophysiology; entorhinal cortex; grid cells; hypoactivity; neurofibrillary tangles; neuronal loss; spatial memory; tau pathology