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.