Hyperinsulinemia provokes synchronous increases in central inflammation and β-amyloid in normal adults

Background: Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (A beta). Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network. Objectives: To determine the effects of induced hyperinsulinemia with euglycemia on A beta, transthyretin, and inflammatory markers and modulators in plasma and cerebrospinal fluid (CSF). Design: Randomized crossover trial. Setting: Veterans Affairs hospital clinical research unit. Participants: Sixteen healthy adults ranging from 55 to 81 years of age (mean age, 68.2 years). Interventions: On separate mornings, fasting participants received randomized infusions of saline or insulin (1.0 mU center dot kg(-1) center dot min(-1)) with variable dextrose levels to maintain euglycemia, achieving plasma insulin levels typical of insulin resistance. Plasma and CSF were collected after an approximately 105-minute infusion. Main Outcome Measures: Plasma and CSF levels of interleukin 1 alpha, interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, F-2-isoprostane (CSF only), A beta, norepinephrine, transthyretin, and apolipoprotein E. Conclusion: Moderate hyperinsulinemia can elevate inflammatory markers and A beta 42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease.