Exp Mol Med.  2015 Mar;47(3):e149. 10.1038/emm.2015.3.

Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome

• Kim B
• Feldman EL

• KMID: 2155414
• DOI: http://doi.org/10.1038/emm.2015.3

Abstract

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer's disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and AD patients exhibit impaired insulin signaling that is similar to that observed in MetS. As we face an alarming increase in obesity and T2D in all age groups, understanding the relationship between MetS and AD is vital for the identification of potential therapeutic targets. Recently, several diabetes therapies that enhance insulin signaling are being tested for a potential therapeutic benefit in AD and dementia. In this review, we will discuss MetS as a risk factor for AD, focusing on IR and the recent progress and future directions of insulin-based therapies.

MeSH Terms

Alzheimer Disease/etiology/metabolism
Amyloid beta-Peptides/metabolism
Animals
Brain/metabolism
Cognition Disorders/*etiology/*metabolism
Humans
Insulin/metabolism
*Insulin Resistance
Metabolic Syndrome X/complications/drug therapy/*metabolism
Molecular Targeted Therapy
Signal Transduction/drug effects
tau Proteins/metabolism
Amyloid beta-Peptides
Insulin
tau Proteins