The nature, significance, and glucagon-like peptide-1 analog treatment of brain insulin resistance in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disease leading over the course of decades to the most common form of dementia. Many of its pathologic features and cognitive deficits may be due in part to brain insulin resistance recently demonstrated in the insulin receptor→insulin receptor substrate-1 (IRS-1) signaling pathway. The proximal cause of such resistance in AD dementia and amnestic mild cognitive impairment (aMCI) appears to be serine inhibition of IRS-1, a phenomenon likely due to microglial release of inflammatory cytokines triggered by oligomeric Aβ. Studies on animal models of AD and on human brain tissue from MCI cases at high risk of AD dementia have shown that brain insulin resistance and many other pathologic features and symptoms of AD may be greatly reduced or even reversed by treatment with FDA-approved glucagon-like peptide-1 (GLP-1) analogs such as liraglutide (Victoza). These findings call attention to the need for further basic, translational, and clinical studies on GLP-1 analogs as promising AD therapeutics.

• Authors: Konrad Talbot, Hoau-Yan Wang
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 10 Issue 1 Suppl Pg. S12-25 (Feb 2014) ISSN: 1552-5279 [Electronic] United States
• PMID: 24529520 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Glucagon-Like Peptide 1

Topics

• Alzheimer Disease (drug therapy, pathology, physiopathology)
• Animals
• Brain (drug effects, metabolism)
• Glucagon-Like Peptide 1 (therapeutic use)
• Humans
• Insulin Resistance