Brain health in the elderly is of special significance since age is associated with increased likelihood of neurodegenerative diseases that cause memory impairment, behavioral and learning deficits. The protein amyloid beta, found in the brain, plays an important physiological role in neuronal function, but an excess of the protein due to aging and disease can damage the central nervous system and impair normal brain function. Though the extracellular deposition of amyloid beta is a signature pathology of AD, the signaling events that trigger aggregation and plaque deposits in the brain are not clear. Research from our laboratory and others have studied amyloid beta extensively and discovered a novel role for the protein as an antimicrobial protein—an innate immune peptide that is part of a defense system against pathogens and microbes. Further, data from our lab and the literature also indicate the presence of numerous microbes in the brain of aged healthy controls and AD patients who have an altered microbial pattern. Our proposal aims to investigate whether the brain can be a niche for microbes. Additionally, we would like to characterize different sources of both control and AD postmortem samples to explore how microbes can penetrate the brain. Findings from this project will serve as translational research for the increasingly aged population and will help in determining disease-modifying therapies to age-related neurological problems to those who suffer from dementia.