The scope of our project is based on the potential role of infectious agents in the cognitive decline of Alzheimer’s disease (AD). We hypothesize that microbial cells and fragments emanating from our normal microbiota gain access to neural tissues over time and promote inflammation, leading to loss of brain tissue integrity. Our approach will be to investigate whether vaccination against a highly conserved microbial surface polysaccharide, poly-N-acetyl glucosamine (PNAG), will impact the neurodegenerative decline in an aggressive mouse model of AD. We also will determine whether PNAG is associated with the brain pathology in this mouse model of AD. Success will support human trials of a vaccine or anti-body to PNAG, in an appropriate clinical setting, to halt cognitive decline.