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| Subject Categories: Proteins | Molecular Biology of Disease |
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| The EMBO Journal
(2007) 26, 5143–5152, doi:10.1038/sj.emboj.7601917 Published online 15 November 2007 |
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| Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau |
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| Tetsuya Kimura, Shunji Yamashita, Tetsuya Fukuda, Jun-Mi Park, Miyuki Murayama, Tatsuya Mizoroki, Yuji Yoshiike, Naruhiko Sahara and Akihiko Takashima |
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Laboratorty for Alzheimer's Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan To whom correspondence should be addressed Akihiko Takashima, Laboratory for Alzheimer's Disease, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Tel: +81 48 467 9627; Fax: +81 48 467 5916; E-mail: kenneth@brain.riken.jp Received 5 July 2007; Accepted 17 October 2007; Published online 15 November 2007. |
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| Abstract |
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| 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). |
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| Keywords: aging, learning and memory, Mn-enhanced MRI, Tau phosphorylation, transgenic mouse |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHNature Genetics Letter (01 Aug 2000) Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration Nature Letters to Editor (31 Jul 2003) The EMBO Journal Article (15 Jan 2001) |
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