New animal models of Alzheimer's disease that display insulin desensitization in the brain

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder, which involves many underlying pathological processes. Recently, it has been demonstrated that AD also includes impairments of insulin signaling in the brain. Type 2 diabetes is a risk factor for AD, and AD and diabetes share a number of pathologies. The classical hallmarks of AD are senile plaques and neurofibrillary tangles, which consist of amyloid-β and hyperphosphorylated tau. Based on the two hallmarks, transgenic animal models of AD have been developed, which express mutant human genes of amyloid precursor protein, presenilin-1/2, and tau. It is likely that these mouse models are too limited in their pathology. In this work, we describe mouse models that model diabetes and show insulin signaling impairment as well as neurodegenerative pathologies that are similar to those seen in the brains of AD patients. The combination of traditional AD mouse models with induced insulin impairments in the brain may be a more complete model of AD. Interestingly, AD mouse models treated with drugs that have been developed to cure type 2 diabetes have shown impressive outcomes. Based on these findings, several ongoing clinical trials are testing long lasting insulin analogues or GLP-1 mimetics in patients with AD.