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Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild‐type human tau
Author(s) -
Kimura Tetsuya,
Yamashita Shunji,
Fukuda Tetsuya,
Park JunMi,
Murayama Miyuki,
Mizoroki Tatsuya,
Yoshiike Yuji,
Sahara Naruhiko,
Takashima Akihiko
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601917
Subject(s) - biology , neuroscience , cortex (anatomy) , tau protein , microbiology and biotechnology , alzheimer's disease , medicine , disease
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).