Systemic administration of fibroblast growth factor-2 (FGF2) reduces BACE1 expression and amyloid pathology in APP23 mice

Neurobiol Aging. 2015 Feb;36(2):821-31. doi: 10.1016/j.neurobiolaging.2014.10.004. Epub 2014 Oct 13.


There is an emerging evidence that growth factors may have a potential beneficial use in the treatment of Alzheimer's disease (AD) because of their neuroprotective properties and effects on neuronal proliferation. Basic fibroblast growth factor or fibroblast growth factor-2 (FGF2) is an anti-inflammatory, angiogenic, and neurotrophic factor that is expressed in many cell types, including neurons and glial cells. Here, we explored whether subcutaneous administration of FGF2 could have therapeutic effects in the APP 23 transgenic mouse, a model of amyloid pathology. FGF2 treatment attenuated spatial memory deficits, reduced amyloid-β (Aβ) and tau pathologies, decreased inducible nitric oxide synthase expression, and increased the number of astrocytes in the dentate gyrus in APP 23 mice compared with the vehicle-treated controls. The decrease in Aβ deposition was associated with a reduction in the expression of BACE1, the main enzyme responsible for Aβ generation. These results were confirmed in a neuroblastoma cell line, which demonstrated that incubation with FGF2 regulates BACE1 transcription. In addition, and in contrast with what has been previously published, the levels of FGF2 were reduced in postmortem brains from AD patients compared with controls. These data, therefore, suggest that systemic administration of FGF2 could have a potential therapeutic application in AD.

Keywords: Alzheimer's disease; Amyloid-β; BACE1; Cell differentiation; Growth factor; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid Precursor Protein Secretases / genetics*
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Aspartic Acid Endopeptidases / genetics*
  • Aspartic Acid Endopeptidases / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Cell Line
  • Disease Models, Animal
  • Female
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression / drug effects*
  • Humans
  • Injections, Subcutaneous
  • Male
  • Mice, Transgenic
  • Transcription, Genetic / drug effects
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • tau Proteins
  • Fibroblast Growth Factor 2
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse