Article
- The EMBO Journal (2007) 26, 5143 - 5152
- doi:10.1038/sj.emboj.7601917
Published online: 15 November 2007
Subject Categories:
Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau
Tetsuya Kimura1, Shunji Yamashita1, Tetsuya Fukuda1, Jun-Mi Park1, Miyuki Murayama1, Tatsuya Mizoroki1, Yuji Yoshiike1, Naruhiko Sahara1 and Akihiko Takashima1
- Laboratorty for Alzheimer's Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan
Correspondence to:
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
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).
Keywords:
- aging,
- learning and memory,
- Mn-enhanced MRI,
- Tau phosphorylation,
- transgenic mouse
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
RESEARCH
Nature Genetics Letter (01 Aug 2000)
Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration
Nature Letters to Editor (31 Jul 2003)
