APOE and Alzheimer disease: However, when neurons were cultured with microglia depleted of lipid-associated apolipoprotein E expression, the neuroprotective phenotype was lost (Qin et al., 2006), implying that the neuroprotective phenotype of microglia in AD is related to apolipoprotein E. In neuron-microglia co-cultures, the activation of the Xc- system by the Aβ deposits not only exacerbates excitotoxicity, but also lowers the neuronal threshold for glutamate toxicity, allowing non-toxic concentrations of glutamate to exert excitotoxic actions (Qin et al., 2006).