Alzheimer’s: the first triple-transgenic mouse
The first triple-transgenic mouse to develop both amyloid-β plaques and tangles of hyperphosphorilated tau protein in Alzheimer’s disease relevant brain regions has been described in a recent issue of Neuron. La Ferla’s team developed a mouse that encodes mutant forms of human amyloid precursor protein, tau and presenilin-1. In their interesting work (Oddo S. et al. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39, 409-421, 2003) the authors demonstrate a localized and specific synaptic dysfunction correlated with the cognitive decline occurring in transgenic mice as well as in Alzheimer’s disease. In particular in the CA1 Hippocampal region, synaptic long-term potentiation (LTP) was severely impaired. LTP is strongly related to memory and learning, thus its deficit in CA1 appears as a pathological basis of cognitive impairment in Alzheimer’s patients.