Challenge of Complexity
Age-associated neurodegenerative diseases are multifactorial, complex and dynamic. As a disease progresses, so do pathways that are activated and the multiple systems of biology that interact. There are no simple A leads to B mechanisms.
While complex, their etiologies share a number of common features; emergence during aging, a prodromal phase beginning in late midlife, genetic predispositions, gender differences in prevalence, and an energy crisis in the brain.
Coincident with the known start of the prodromal phase are endocrine transitions states; periods associated with neural restructuring and declining bioenergetic capacity of the brain.
A one fuel organ, the brain relies almost exclusively on glucose; making it particularly vulnerable to even modest declines in glucose; suggesting that the decline in glucose may act as a common initiating mechanism to unmask and amplify existing risk factors.
Responding to this challenge we launched a pan-disease systems biology initiative using human derived stem cells and translatable animal models designed to capture the complexity of human risk factors and disease. We are systematically characterizing (mapping) these models, across the full analytical spectrum from the molecular and multi-omics level through to biological, immunological and functional phenotypes. Outputs of these assays are being integrated through computational systems biology network and pathway analytics to derive both common vs unique disease initiating mechanisms.
These data will provide us with a new and enriched set of targets to pursue in our quest to create Innovations in Brain Science of the Future for Those Who Need a Cure Today.