Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

D. Allan Butterfield, Fabio Di Domenico, Eugenio Barone

Research output: Contribution to journalReview articlepeer-review

298 Scopus citations

Abstract

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5. years after 65. years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggests that oxidative stress plays a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data interpreted from the point of view of oxidative stress with the aim of highlighting progresses in this field.

Original languageEnglish
Pages (from-to)1693-1706
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1842
Issue number9
DOIs
StatePublished - Sep 2014

Bibliographical note

Funding Information:
This was supported by NIH grant AG-05119 to D.A.B. and funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007–2013) under REA grant agreement no. 624341 to E.B.

Keywords

  • Alzheimer disease
  • Heme oxygenase 1 and biliverdin reductase
  • Insulin
  • Oxidative stress
  • Protein oxidation
  • Type-2 diabetes mellitus and insulin resistance

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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