Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice

Transl Psychiatry. 2013 Dec 3;3(12):e330. doi: 10.1038/tp.2013.102.


Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Case-Control Studies
  • Disease Models, Animal
  • Early Diagnosis
  • Electroencephalography / drug effects*
  • Humans
  • Insulin-Like Growth Factor I / cerebrospinal fluid
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Macaca
  • Mice


  • IGF1 protein, human
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I