TLR9 and early-onset autosomal dominant Alzheimer disease: Both LPS and curli are potent stimulators of TLR4 or TLR2, respectively;18 while the DNA that irreversibly complexes with curli during biofilm formation activates TLR9.23 Studies in human Alzheimer’s disease and Parkinson’s disease suggest direct interaction between amyloid-β or α-synuclein aggregates and the UPR even when added exogenously and outside of the ER itself.53–56 Given that curli is structurally similar to human amyloids57 and can escape the endosome and localize in the cytosol of macrophages after uptake,17,23 we asked if it could directly interact with the UPR.