Targeting Shared Mechanisms in Neurodegenerative and Metabolic Disease

A growing body of evidence indicates that obesity in mid-life increases the risk of dementia later in life, and that interventions that reduce obesity can be neuroprotective. This project aims to understand these links in order to find interventions that can more potently slow or delay neurodegeneration in mice, and gain molecular understanding between these links using human stem cell-derived cellular models. In addition, the team is developing a novel model of diet-induced neuroinflammation to map the temporal progression of inflammatory processes induced by a physiologically relevant insult.

The team generated over a thousand samples exploring how diet affects the mouse brain and intersects with pathways implicated in neurodegeneration. Using a prion mouse model, they confirmed the neuroprotective effects of some anti-obesity drugs and are using computational methods to predict novel treatment strategies. Additionally, to underpin community science efforts to model neurodegenerative disease with iPSC-derived cell types, the team and other members of the NDCN have identified a common reference iPSC line.