High TLR4 immunoreactivity was observed in glial cells surrounding plaques in postmortem brains of AD patients (Walter et al., 2007), and significantly higher levels of pro-inflammatory cytokines have been detected in the brains of APP/PS1 mice compared to TLR4-mutant APP/PS1 mice (Jin et al., 2008). Here, PSEN1 is linked to Alzheimer disease.