"Much ado has been made of the neuronal damage inflicted by aggregates of tau, but what about the cost of losing normal tau protein to these proteopathic snarls? In the June 26 Journal of Experimental Medicine, researchers led by David Blum of the University of Lille in France made the case that loss of tau function triggers insulin resistance in the brain. In tau knockout mice, hippocampal neurons responded sluggishly to insulin, laying low synaptic plasticity. Metabolic disturbances extended beyond the brain: The mice overate, were obese, and tolerated glucose poorly. The researchers proposed that loss of normal tau function in early stages of Alzheimer’s could explain the brain insulin resistance observed in some people with the disease. They claim it could even contribute to systemic metabolic disorders—such as Type 2 diabetes—that emerge prior to cognitive symptoms."