Serum but not cerebrospinal fluid levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) are increased in Alzheimer's disease

Psychoneuroendocrinology. 2013 Sep;38(9):1729-37. doi: 10.1016/j.psyneuen.2013.02.006. Epub 2013 Mar 6.


Background: Although insulin-like growth factor-I (IGF-I) is of importance for the adult function of the central nervous system (CNS), little is known of the significance of IGF-I in cerebrospinal fluid (CSF) in relation to Alzheimer's disease (AD).

Methods: A cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), or other dementias (n=15). IGF-I, IGF-binding protein-3 (IGFBP-3), and insulin were measured in serum and CSF.

Results: Serum IGF-I level was increased in AD patients and in patients with other dementias compared to healthy controls (P=0.01 and P<0.05, respectively). Serum IGFBP-3 concentration was increased in AD and SMCI patients compared to controls (P=0.001 and P<0.05, respectively). CSF levels of IGF-I and IGFBP-3 as well as serum and CSF levels of insulin were similar in all study groups. In the total study population (n=80), serum levels of IGF-I and IGFBP-3 correlated negatively with CSF β-amyloid₁₋₄₂ (Aβ₁₋₄₂) level (r=-0.29, P=0.01 and r=-0.27, P=0.02, respectively) and in the AD patients (n=32), the increased CSF/serum IGF-I ratio correlated positively with the CSF level of phosphorylated tau protein (P-tau; r=0.42, P=0.02).

Conclusion: Patients with AD as well as other dementias had high levels of IGF-I in serum but not in CSF. In AD patients, the IGF-I system was associated with biomarkers of AD disease status.

Keywords: AD biomarker; Alzheimer's disease; Cerebrospinal fluid; IGF-I; IGFBP-3; Insulin; Mild cognitive impairment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Body Mass Index
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cross-Sectional Studies
  • Dementia / blood
  • Dementia / cerebrospinal fluid
  • Female
  • Humans
  • Insulin / blood
  • Insulin / cerebrospinal fluid
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / cerebrospinal fluid
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor I / cerebrospinal fluid
  • Insulin-Like Growth Factor I / physiology
  • Male
  • Peptide Fragments / cerebrospinal fluid
  • Single-Blind Method
  • Waist-Hip Ratio
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • IGFBP3 protein, human
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Insulin-Like Growth Factor I