Insulin Signaling Impairment in the Brain as a Risk Factor in Alzheimer's Disease

Type 2 diabetes is a risk factor for developing Alzheimer's disease (AD). The underlying mechanism that links up the two conditions seems to be the de-sensitization of insulin signaling. In patients with AD, insulin signaling was found to be de-sensitized in the brain, even if they did not have diabetes. Insulin is an important growth factor that regulates cell growth, energy utilization, mitochondrial function and replacement, autophagy, oxidative stress management, synaptic plasticity, and cognitive function. Insulin desensitization, therefore, can enhance the risk of developing neurological disorders in later life. Other risk factors, such as high blood pressure or brain injury, also enhance the likelihood of developing AD. All these risk factors have one thing in common - they induce a chronic inflammation response in the brain. Pro-inflammatory cytokines block growth factor signaling and enhance oxidative stress. The underlying molecular processes for this are described in the review. Treatments to re-sensitize insulin signaling in the brain are also described, such as nasal insulin tests in AD patients, or treatments with re-sensitizing hormones, such as leptin, ghrelin, glucagon-like peptide 1 (GLP-1),and glucose-dependent insulinotropic polypeptide (GIP). The first clinical trials show promising results and are a proof of concept that utilizing such treatments is valid.