Grant: Project Grant

Alzheimer's disease (AD) is a debilitating condition leading to severe memory loss and cognitive decline. Recent research indicates that gut microbiota - the bacteria in our intestines - may influence AD development through the gut-brain axis. An imbalance in these bacteria can lead to harmful substances that contribute to neuro-inflammation and the buildup of amyloid plaques and tau proteins, key factors in AD. This project explores whether probiotics - beneficial bacteria - can prevent or slow AD progression. Unlike treatments focusing on amyloid plaques, we target tau proteins, more closely linked to cognitive decline in AD. Probiotics may reduce tau hyperphosphorylation by suppressing the enzyme GSK-3b and reducing brain inflammation. We developed a unique rat model that mimics early human tau pathology by introducing pretangle tau into the locus coeruleus (LC) of the brain, resulting in symptoms similar to early stage of AD, such as smell and spatial memory problems, and LC nerve fiber loss. Our study will test whether probiotics can improve gut bacteria and brain function in this model with three goals: 1) to determine if probiotics prevent or reduce behavioral problems in tau model rats, 2) to see if enhancing gut microbiota reduces tau pathology, and 3) to find out if probiotics change gene expression in the brain. We believe introducing healthy bacteria into the gut will lower neuroinflammation and improve cognitive function by reducing tau pathology. To test this, we will infuse a gene for pretangle tau into the LC of rats, then feed them probiotic-enriched water. We will conduct behavioral tests, followed by blood and brain assays to measure tau pathology and brain health. Our project is based on strong preliminary data showing probiotic supplements improve spatial learning and alter gut microbiota in our rat model. Our team is well-equipped to carry out this research, potentially leading to a new, non-invasive strategy for delaying AD through diet.