Abstract Early Alzheimer’s disease (AD) diagnosis may improve its management and slow disease progression. Developing new biomarkers complementing existing diagnostic tools can potentially contribute to early AD diagnosis and risk prediction. IgG antibodies against selected periodontal microorganisms remain elevated in the blood for up to 15 years following exposure and precede the development of cognitive impairment by several years. IgG antibodies against periodontal microorganisms may therefore be useful novel biomarkers of AD. We have reported that empirically derived groups of IgG antibodies against 19 periodontal microorganisms consistently predicted all-cause, cardiovascular and cancer mortality in the National Health and Nutrition Examination Study 3 (NHANES 3) follow-up. In the present application we propose to evaluate the association between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and Alzheimer’s disease mortality and cognitive impairment in the NHANES 3 data. The results of this study will open up AD prevention strategies by identifying potentially novel biomarkers to predict AD years before it develops and provide mechanistic insights linking the human microbiome to AD and cognition.