Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau.
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).
Kimura
Tetsuya
T
Laboratorty for Alzheimer's Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan.
Yamashita
Shunji
S
Fukuda
Tetsuya
T
Park
Jun-Mi
JM
Murayama
Miyuki
M
Mizoroki
Tatsuya
T
Yoshiike
Yuji
Y
Sahara
Naruhiko
N
Takashima
Akihiko
A
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*
D016875:tau Proteins