title: Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults.
abstract: BACKGROUND
  Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (Abeta). 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.
  
  
  OBJECTIVE
  To determine the effects of induced hyperinsulinemia with euglycemia on Abeta, transthyretin, and inflammatory markers and modulators in plasma and cerebrospinal fluid (CSF).
  
  
  METHODS
  Randomized crossover trial.
  
  
  METHODS
  Veterans Affairs hospital clinical research unit.
  
  
  METHODS
  Sixteen healthy adults ranging from 55 to 81 years of age (mean age, 68.2 years).
  
  
  METHODS
  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.
  
  
  METHODS
  Plasma and CSF levels of interleukin 1alpha, interleukin 1beta, interleukin 6, tumor necrosis factor alpha, F2-isoprostane (CSF only), Abeta, norepinephrine, transthyretin, and apolipoprotein E.
  
  
  RESULTS
  Insulin increased CSF levels of F2-isoprostane and cytokines (both P<.01), as well as plasma and CSF levels of Abeta42 (both P<.05). The changes in CSF levels of Abeta42 were predicted by increased F2-isoprostane and cytokine levels (both P<.01) and reduced transthyretin levels (P = .02). Increased inflammation was modulated by insulin-induced changes in CSF levels of norepinephrine and apolipoprotein E (both P<.05).
  
  
  CONCLUSIONS
  Moderate hyperinsulinemia can elevate inflammatory markers and Abeta42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease.
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA 98108, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Fishel
authors.forename: G Stennis
authors.initials: GS
authors.lastname: Watson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Pattie S
authors.initials: PS
authors.lastname: Green
authors.forename: J Jacob
authors.initials: JJ
authors.lastname: Kulstad
authors.forename: David G
authors.initials: DG
authors.lastname: Cook
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.forename: Dmitry
authors.initials: D
authors.lastname: Goldgaber
authors.forename: Wei
authors.initials: W
authors.lastname: Nie
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Plymate
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001057:Apolipoproteins E / Q000097:blood / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000032:analysis*; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000134:cerebrospinal fluid; D007375:Interleukin-1 / Q000097:blood / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000134:cerebrospinal fluid; D011228:Prealbumin / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016207:Cytokines; D028441:F2-Isoprostanes; D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D011228:Prealbumin; D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine