Format

Send to

Choose Destination
Alzheimers Dement. 2014 Feb;10(1 Suppl):S26-32. doi: 10.1016/j.jalz.2013.12.004.

How does brain insulin resistance develop in Alzheimer's disease?

Author information

1
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: felice@bioqmed.ufrj.br.
2
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signaling on cognition. Discoveries summarized here provide pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD.

KEYWORDS:

Alzheimer's disease; Amyloid-β oligomers; GLP-1R agonists; Insulin resistance; Insulin therapy

PMID:
24529521
DOI:
10.1016/j.jalz.2013.12.004
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center