Two recent studies have carefully characterized amyloid-related brain insulin resistance in animal models of, and patients with, Alzheimer disease (AD). The researchers show that exendin-4, a glucagon-like peptide 1 receptor agonist, ameliorates pathology and symptoms in a mouse model of AD, suggesting a novel therapeutic approach to this disease.
Your institute does not have access to this article
Open Access articles citing this article.
Molecular Brain Open Access 25 March 2019
Molecular Brain Open Access 01 August 2017
Acta Neuropathologica Communications Open Access 17 September 2016
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Hoyer, S. & Nitsch, R. Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type. J. Neural. Transm. 75, 227–232 (1989).
Talbot, K. et al. Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J. Clin. Invest. 122, 1316–1338 (2012).
Bomfim, T. R. et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated Aβ oligomers. J. Clin. Invest. 122, 1339–1353 (2012).
Ma, Q.-L. et al. β-Amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J. Neurosci. 29, 9078–9089 (2009).
Cao, D., Lu, H., Lewis, T. L. & Li, L. Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J. Biol. Chem. 282, 36275–36282 (2007).
Ho, L. et al. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. FASEB J. 18, 902–904 (2004).
Zhao, L. et al. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J. Neurosci. 24, 11120–11126 (2004).
Sivertsen, J., Rosenmeier, J., Holst, J. J. & Vilsboll, T. The effect of glucagon-like peptide 1 on cardiovascular risk. Nat. Rev. Cardiol. 9, 209–222 (2012).
Craft, S. et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch. Neurol. 69, 29–38 (2012).
S. Craft receives research support from Kurve Technology in the form of insulin delivery devices.
About this article
Cite this article
Craft, S. Insulin resistance and AD—extending the translational path. Nat Rev Neurol 8, 360–362 (2012). https://doi.org/10.1038/nrneurol.2012.112
Molecular Brain (2019)
Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation
Molecular Neurobiology (2019)
Cross-fibrillation of insulin and amyloid β on chiral surfaces: Chirality affects aggregation kinetics and cytotoxicity
Nano Research (2018)
Peripheral and Central Effects of Memantine in a Mixed Preclinical Mice Model of Obesity and Familial Alzheimer’s Disease
Molecular Neurobiology (2018)