This approach has already obtained promising results by identifying novel lifespan extending genes in yeast, which were then experimentally validated. Here, we perform a systematic knockout of each gene in the human PND-1186 metabolic network and predict which knockouts will most likely transform the AD metabolic state back closer to the healthy one. The pathways enriched with reactions whose knockout is predicted by MTA to reverse AD��s key metabolic alterations back closer to the healthy state are Vitamin D, nucleotides and Steroid metabolism. Vitamin D has been studied in recent years for its relation to cognitive performance and AD, but its associations remain uncertain. Nevertheless, it has been increasingly recognized to play an active role in the nervous system, and a genome-wide association study of late-onset AD found evidence for involvement of the vitamin D receptor. Steroid metabolism is another pathway we found enriched with predicted drug targets for AD. Intriguingly, the reaction that received the highest score within this pathway is 11-beta-hydroxysteroid dehydrogenase type 1, an enzyme that catalyzes the intracellular regeneration of active glucocorticoids. 11b-HSD1 knock-out mice have shown improved cognition, and 11b-HSD1 inhibitors improved memory in elderly men. In general, steroids offer 2′-deoxy-2′-Fluorouridine interesting therapeutic opportunities because of their varying roles in the nervous system: they regulate neurotransmitter systems, they promote the viability of neurons, and they influence cognitive processes. In the current study, we used genome scale metabolic modeling approaches to integrate gene expression measurements in the cortex of AD patients to address three key research questions: what are the main metabolic alterations occurring in AD? Which metabolites may serve as candidates for metabolic biomarkers of AD in the CSF and in the blood? And finally, which metabolic genes may be silenced to most efficiently reverse the metabolic alterations observed in AD to a state of healthy aged matched controls? We described the metabolic alterations in AD in both the cortex and blood leukocytes. The cortical analysis was based on a very large dataset of AD and control patients.