PSEN1 and Alzheimer disease: In transgenic mice expressing AD-causing mutant forms of APP and PSEN1 (APP/PS1), astrocytes surrounding Aβ plaques have lower levels of EAAT2, which leads to an extra-synaptic accumulation of glutamate, neuronal hyperactivity [110] potentially mediated by neuronal NMDA receptors [111], and possibly neurotoxicity.