Our initial findings from AD mouse models provide the first in vivo evidence that stimulation of innate immunity via TLR9 with CpG ODN appears to reduce behavioral deficits and restrict all pathological hallmarks of AD, including amyloid plaques, tau pathology, and CAA without associated toxicity (Scholtzova et al., 2009, 2014, 2017). Here, TLR9 is linked to Alzheimer disease.