Serum Insulin-Like Growth Factor I Deficiency Associates to Alzheimer's Disease Co-Morbidities

J Alzheimers Dis. 2019;69(4):979-987. doi: 10.3233/JAD-190241.


Increasing evidence supports the notion that Alzheimer's disease (AD), a condition that presents heterogeneous pathological disturbances, is also associated to perturbed metabolic function affecting insulin and insulin-like growth factor I (IGF-I). While impaired insulin activity leading to insulin resistance has been associated to AD, whether altered IGF-I function affects the disease is not entirely clear. Despite the limitations of mouse models to mimic AD pathology, we took advantage that serum IGF-I deficient mice (LID mice) present many functional perturbations present in AD, most prominently cognitive loss, which is reversed by treatment with systemic IGF-I. We analyzed whether these mice display other pathological traits that are usual co-morbidities of AD. We found that LID mice not only display cognitive disturbances, but also show altered mood and sociability, increased susceptibility to epileptiform activity, and a disturbed sleep/wake cycle. Collectively, these data suggest that reduced IGF-I activity contributes to heterogeneous deficits commonly associated to AD. We suggest that impaired IGF-I activity needs to be taken into consideration when modeling this condition.

Keywords: Alzheimer’s disease; animal models of disease; co-morbidities; insulin-like growth factor 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / etiology*
  • Animals
  • Cognition Disorders / complications
  • Disease Models, Animal
  • Female
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / deficiency*
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mood Disorders / complications
  • Social Behavior


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