"most recently, we have shown that bdnf appears to be a major player not only in central metabolic pathways but also as a regulator of metabolism in skeletal muscle. hippocampal samples from alzheimer’s disease donors show decreased bdnf expression and individuals with alzheimer’s disease have low plasma levels of bdnf. also, patients with major depression have lower levels of serum bdnf than normal control subjects. other studies suggest that plasma bdnf is a biomarker of impaired memory and general cognitive function in ageing women and a low circulating bdnf level was recently shown to be an independent and robust biomarker of mortality risk in old women. low levels of circulating bdnf are also found in obese individuals and those with type 2 diabetes. in addition, we have demonstrated that there is a cerebral output of bdnf and that this is inhibited during hyperglycaemic clamp conditions in humans. this last finding may explain the concomitant finding of low circulating levels of bdnf in individuals with type 2 diabetes, and the association between low plasma bdnf and the severity of insulin resistance.