Pre-diabetic AD mice, modeled in APP/PS1 mice fed a high fat diet, had significant neuronal loss, and APP/PS1 mice crossed with an obesity driven type 2 diabetes model (db/db) had even greater neuronal loss and decreased synaptic density (45), supporting the link between metabolic dysfunction and cognitive decline. The gene discussed is APP; the disease is obesity due to melanocortin 4 receptor deficiency.