Targeting Insulin Resistance for the Treatment of Alzheimer’s Disease: From Laboratory to the Clinic

Alzheimer's disease (AD) is reaching epidemic levels as the aged population increases. Despite tremendous efforts, no disease-modifying drug is currently available. Mounting epidemiological and basic science evidence links AD and type-2 diabetes mellitus (T2DM). Impairment in insulin receptor transduction pathways affects metabolism of amyloid precursor protein and the balanced phosphorylation of tau protein, two critical players in AD pathology. Furthermore, insulin resistance and dysregulated insulin signaling have been observed in the brains of AD patients. Drugs currently used to treat T2DM improve cognition and brain insulin signaling in rodent AD models, both in vitro and in vivo. Intranasal insulin and two drugs currently used to treat T2DM, metformin and the incretin hormone Exendin-4, a glucagon-like peptide-1 (GLP-1) agonist, are currently in clinical trials for mild cognitive impairment (MCI) and AD. This symposium will highlight the role of insulin resistance in AD, review recent preclinical data supporting the use of antidiabetic drugs to ameliorate AD pathology, and explore the current status of clinical trials using insulin and insulin-sensitizing agents for the treatment of AD.

(Courtesy of Alzheimer’s Disease tangles, via srxawordonhealth.com)