Title: Dietary Fiber’s Effect on Alzheimer’s Biomarker Development: A Metabolomic Approach
Abstract: It has been well documented in recent Alzheimer’s research that dietary fiber intake has protective effects against Alzheimer’s disease development. We propose that the mechanism for this effect operates through the breakdown of neurologically protective fiber-derived metabolites . To explore this, we utilized longitudinal data from 877 participants enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) study to perform a mediation analysis. Participants were initially aged 40-65 and free from dementia. We evaluated a calculated Total Fiber Score, a composite score based on the number of servings per week an individual had of 6 different fiber sources, as the exposure, fiber-derived metabolite levels as the mediator, and plasma Alzheimer’s biomarker levels approximately two years later as the outcomes. We found that, of our eight metabolites, N,N,N-trimethyl-alanylproline betaine had a significant mediating effect with ptau-217 plasma concentration (p=0.004), but the total and direct effects were not statistically significant. In sensitivity analyses controlling for kidney disease status, as this is a metabolite involved in the body’s urea cycle, we still saw this significant mediated effect (p=0.018). Although it cannot be said that this mechanism is strongly causal, we can say that there is a potential association between fiber intake, fiber derived metabolite values, and subsequent Alzheimer’s biomarker levels two years after.
