Supplement to Prebiotics Intervention to Reduce Alzheimer's Disease Risk via Brain-Gut Axis in an APOE4 Mouse Model

Project Summary This is an Administration Supplement application under the parent grant RF1AG062480 entitled “Prebiotics Intervention to Reduce Alzheimer''s Disease (AD) Risk via Brain-Gut Axis in an APOE4 Mouse Model”. In the parent grant, we are looking at APOE4, the strongest genetic risk factor for AD; in this Supplement, we propose to further look into another risk factor of AD- traumatic brain injury (TBI). Our goal is to determine if administrating prebiotic Inulin diet before TBI in young mice would protect the brain vascular, metabolic, and white matter (WM) integrity and reduce neuroinflammation through gut microbiome modulation. The central hypothesis is that prebiotic inulin diet is protective to brain vascular, metabolic and WM integrity, which is associated with gut microbiome modulation. We will test the hypothesis by pursuing the following two Specific Aims: (i) Determine protective effects of inulin on the gut microbiome and SCFAs production in TBI; (ii) Identify protective effects of inulin on brain functions and neuroinflammation in TBI. The success of the study would enhance our understanding of CNS-peripheral interactions in TBI. As Inulin-related diets are commercially available, and MRI neuroimaging and gut microbiome analyses are readily to be used for humans, our approaches are highly translational; therefore, we would be able to rapidly move to clinical studies for TBI patients in the future.