Although TLR5 expression in human and mouse microglia was previously described [4, 52], and a few studies recently reported on a functional relevance for this receptor in the setting of various CNS disorders including neuropathic pain, stroke, and Alzheimer’s disease (AD) [7, 24, 33, 64], its mode of action and functional consequences of this receptor activation in the brain has not been explored. Here, TLR5 is linked to Alzheimer disease.