title: Mechanisms of brain aging regulation by insulin: implications for neurodegeneration in late-onset Alzheimer's disease.
abstract: Insulin and IGF seem to be important players in modulating brain aging. Neurons share more similarities with islet cells than any other human cell type. Insulin and insulin receptors are diffusely found in the brain, especially so in the hippocampus. Caloric restriction decreases insulin resistance, and it is the only proven mechanism to expand lifespan. Conversely, insulin resistance increases with age, obesity, and sedentarism, all of which have been shown to be risk factors for late-onset Alzheimer's disease (AD). Hyperphagia and obesity potentiate the production of oxidative reactive species (ROS), and chronic hyperglycemia accelerates the formation of advanced glucose end products (AGEs) in (pre)diabetes-both mechanisms favoring a neurodegenerative milieu. Prolonged high cerebral insulin concentrations cause microvascular endothelium proliferation, chronic hypoperfusion, and energy deficit, triggering β-amyloid oligomerization and tau hyperphosphorylation. Insulin-degrading enzyme (IDE) seems to be the main mechanism in clearing β-amyloid from the brain. Hyperinsulinemic states may deviate IDE utilization towards insulin processing, decreasing β-amyloid degradation.
authors.affiliation: Division of Geriatric Neurology, Department of Neurology, Clinicas Hospital (HCPA), Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos Street 2.350, 90035-903 Porto Alegre, RS, Brazil.
authors.forename: Artur F
authors.initials: AF
authors.lastname: Schuh
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Rieder
authors.forename: Liara
authors.initials: L
authors.lastname: Rizzi
authors.forename: Márcia
authors.initials: M
authors.lastname: Chaves
authors.forename: Matheus
authors.initials: M
authors.lastname: Roriz-Cruz