Impaired peripheral glucose homeostasis and Alzheimer's disease

Alzheimer's disease (AD) is the most common type of dementia. Recent studies suggest that metabolic disturbances, particularly type 2 diabetes (T2D) increase the risk of cognitive decline and AD. AD is also a risk factor for T2D, and a growing body of evidence indicates that these diseases are connected both at clinical and molecular levels. In T2D, peripheral insulin resistance, hyperglycemia and eventually insulin deficiency develops, leading to an overall decline in tissue health. More recently, brain insulin resistance has been shown to be a key feature of AD that is linked to neuronal dysfunction and cognitive impairment. Furthermore, both AD and T2D are amyloidogenic diseases, with abnormal aggregation of amyloid-beta peptide (A beta) and islet amyloid polypeptide (IAPP) respectively contributing to cellular death and disease pathogenesis. Emerging data suggests that A beta may have peripheral effects including its co-deposition in the pancreas. In this review, we discuss how peripheral effects of A beta and metabolic disturbances may impact AD pathogenesis. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.' (C) 2017 Elsevier Ltd. All rights reserved.