Science

Mark A. Fishel, MD; G. Stennis Watson, PhD; Thomas J. Montine, MD, PhD; Qin Wang, PhD; Pattie S. Green, PhD; J. Jacob Kulstad, BS; David G. Cook, PhD; Elaine R. Peskind, MD; Laura D. Baker, PhD; Dmitry Goldgaber, PhD; Wei Nie, MD, PhD; Sanjay Asthana, MD;

Background: Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid. 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 beta-amyloid, 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 · kg-1 · 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, F2-isoprostane (CSF only), beta-amyloid, norepinephrine, transthyretin, and apolipoprotein E.
Results: Insulin increased CSF levels of F2-isoprostane and cytokines (both P