%0 Journal Article %A Marlen Knobloch %A Mélissa Farinelli %A Uwe Konietzko %A Roger M. Nitsch %A Isabelle M. Mansuy %T Aβ Oligomer-Mediated Long-Term Potentiation Impairment Involves Protein Phosphatase 1-Dependent Mechanisms %D 2007 %R 10.1523/JNEUROSCI.0395-07.2007 %J The Journal of Neuroscience %P 7648-7653 %V 27 %N 29 %X Amyloid β (Aβ) oligomers are derived from proteolytic cleavage of amyloid precursor protein (APP) and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. The mechanisms underlying such toxicity on synaptic functions are complex and not fully understood. Here, we provide the first evidence that these mechanisms involve protein phosphatase 1 (PP1). Using a novel transgenic mouse model expressing human APP with the Swedish and Arctic mutations that render Aβ more prone to form oligomers (arcAβ mice), we show that the LTP impairment induced by Aβ oligomers can be fully reversed by PP1 inhibition in vitro. We further demonstrate that the genetic inhibition of endogenous PP1 in vivo confers resistance to Aβ oligomer-mediated toxicity and preserves LTP. Overall, these results reveal that PP1 is a key player in the mechanisms of AD pathology. %U https://www.jneurosci.org/content/jneuro/27/29/7648.full.pdf