Bacterial Traces in Alzheimer’s Brains: Implications for Pathogenic Routes
While Alzheimer’s disease (AD) is a primary neurodegenerative disease, pathomicrobes may contribute to neuroinflammation, amyloid plaque and phosphorylate tau formation, and neuronal damage through multiple mechanisms. We hypothesize that individual AD patients present different pathomicrobes, depending on the host’s susceptibility to certain chronic or repetitious infections. Despite being anatomically proximal to the brain, the eye-brain pathogenic route has not yet been investigated compared to mainstream studies on gut, oral, and nasal evidence. This project aims to seek ocular bacterial traces in postmortem AD brains. We will first detect the paucimicrobial DNAs in frozen samples of the orbitofrontal cortex, the brain region earliest impacted in AD and near the ocular apparatus. Translocated bacterial RNAs will be examined using a novel subcellular spatial transcriptomics method, detecting human brain genes and genes of ocular bacteria in formalin-fixed paraffin-embedded sections of the frontal cortex and dorsal pontine. The laLer structure contains the principal sensory trigeminal nucleus (innervating ocular area), locus coeruleus (impacted early in AD), and nucleus incertus (associated with cognitive functions). This project will provide a pioneering view of contextual brain changes in
AD cases with and without ocular paucimicrobial traces by comparing AD and healthy controls. Further detection of translocated bacterial proteins may be applied with multiplexing imaging. Project outcomes will warrant unique insights into whether the eye-brain pathogenic route contributes to AD, hence facilitating the repurposed translation of ocular findings in developing peripheral biomarkers and preventions for AD. Besides publication, online resources may also be generated for pathogenic-Alzheimer’s disease research community.