Context-sensitive network analysis identifies food metabolites associated with Alzheimer’s disease: an exploratory study

BACKGROUND: Diet plays an important role in Alzheimer’s disease (AD) initiation, progression and outcomes. Previous studies have shown individual food-derived substances may have neuroprotective or neurotoxic effects. However, few works systematically investigate the role of food and food-derived metabolites on the development and progression of AD. METHODS: In this study, we systematically investigated 7569 metabolites and identified AD-associated food metabolites using a novel network-based approach. We constructed a context-sensitive network to integrate heterogeneous chemical and genetic data, and to model context-specific inter-relationships among foods, metabolites, human genes and AD. RESULTS: Our metabolite prioritization algorithm ranked 59 known AD-associated food metabolites within top 4.9%, which is significantly higher than random expectation. Interestingly, a few top-ranked food metabolites were specifically enriched in herbs and spices. Pathway enrichment analysis shows that these top-ranked herb-and-spice metabolites share many common pathways with AD, including the amyloid processing pathway, which is considered as a hallmark in AD-affected brains and has pathological roles in AD development. CONCLUSIONS: Our study represents the first unbiased systems approach to characterizing the effects of food and food-derived metabolites in AD pathogenesis. Our ranking approach prioritizes the known AD-associated food metabolites, and identifies interesting relationships between AD and the food group “herbs and spices”. Overall, our study provides intriguing evidence for the role of diet, as an important environmental factor, in AD etiology.