title: Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau.
abstract: To investigate how tau affects neuronal function during neurofibrillary tangle (NFT) formation, we examined the behavior, neural activity, and neuropathology of mice expressing wild-type human tau. Here, we demonstrate that aged (>20 months old) mice display impaired place learning and memory, even though they do not form NFTs or display neuronal loss. However, soluble hyperphosphorylated tau and synapse loss were found in the same regions. Mn-enhanced MRI showed that the activity of the parahippocampal area is strongly correlated with the decline of memory as assessed by the Morris water maze. Taken together, the accumulation of hyperphosphorylated tau and synapse loss in aged mice, leading to inhibition of neural activity in parahippocampal areas, including the entorhinal cortex, may underlie place learning impairment. Thus, the accumulation of hyperphosphorylated tau that occurs before NFT formation in entorhinal cortex may contribute to the memory problems seen in Alzheimer's disease (AD).
authors.affiliation: Laboratorty for Alzheimer's Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukuda
authors.forename: Jun-Mi
authors.initials: JM
authors.lastname: Park
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murayama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mizoroki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiike
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sahara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001931:Brain Mapping; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins