Does Fructose Contribute to Neurodegeneration and Alzheimer's Disease Development?

We will explore whether the consumption of fructose by our brain’s trash collector, microglia, is a driver of and therapeutic target for neurodegeneration.

Fructose may contribute to the onset and progression of Alzheimer’s Disease (AD), with increased fructose consumption and presence in the brain associated with a higher likelihood of developing AD and worse prognosis, but the how remains unknown. Excitingly, we found that the brain’s garbage collector, microglia, consume fructose but at the cost of their garbage collecting duties. We will explore whether this trade-off is a driver of AD, test whether fructose metabolism is a treatment target, and establish non-invasive imaging of fructose metabolism as a diagnostic and prognostic tool.

Our work is unique because it bridges multiple disparate fields, from basic molecular and cellular biology to engineering and nuclear physics, allowing us to not only identify better ways of treating AD patients but also establish non-invasive diagnostic and prognostic imaging strategies.

We foresee three key benefits that will arise from our work:
1. We will have tested therapeutic approaches with better safety profiles than standard pharmacological approaches. We have identified two clinically feasible food-additive approaches that have exciting therapeutic potential: a compensatory metabolite that drives desired microglia behavior and a metabolite that competitively inhibits fructose transport. The data obtained from our work will inform preclinical work and early-stage clinical trials.
2. We will test whether cell-based therapy with metabolically engineered microglia is a feasible treatment strategy. Recent work has demonstrated that microglia replacement is feasible f