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Title: Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy
Authors: Boekhoorn, Karin ×
Terwel, Dick
Biemans, Barbara
Borghgraef, Peter
Wiegert, Olof
Ramakers, Ger J A
de Vos, Koos
Krugers, Harm
Tomiyama, Takami
Mori, Hiroshi
Joels, Marian
Van Leuven, Freddy
Lucassen, Paul J #
Issue Date: Mar-2006
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:26 issue:13 pages:3514-3523
Abstract: The microtubule binding protein tau is implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by diverse mutations in the tau gene. Hyperphosphorylation of tau is considered crucial in the age-related formation of neurofibrillary tangles (NFTs) correlating well with neurotoxicity and cognitive defects. Transgenic mice expressing FTD mutant tau-P301L recapitulate the human pathology with progressive neuronal impairment and accumulation of NFT. Here, we studied tau-P301L mice for parameters of learning and memory at a young age, before hyperphosphorylation and tauopathy were apparent. Unexpectedly, in young tau-P301L mice, increased long-term potentiation in the dentate gyrus was observed in parallel with improved cognitive performance in object recognition tests. Neither tau phosphorylation, neurogenesis, nor other morphological parameters that were analyzed could account for these cognitive changes. The data demonstrate that learning and memory processes in the hippocampus of young tau-P301L mice are not impaired and actually improved in the absence of marked phosphorylation of human tau. We conclude that protein tau plays an important beneficial role in normal neuronal processes of hippocampal memory, and conversely, that not tau mutations per se, but the ensuing hyperphosphorylation must be critical for cognitive decline in tauopathies.
URI: 
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Associated Laboratories - miscellaneous (-)
× corresponding author
# (joint) last author

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