Towards non invasive nerve growth factor therapies for Alzheimer's disease

J Alzheimers Dis. 2008 Oct;15(2):255-83. doi: 10.3233/jad-2008-15210.


In the past thirty years, nerve growth factor (NGF) has received much attention for its potential role as a therapeutic agent for Alzheimer's disease (AD) due to its neurotrophic activities on basal forebrain cholinergic neurons. This attention has been renewed by recent findings that provide new causal links between defects in NGF signaling, transport or processing to the activation of the amyloidogenic route and, more generally, to AD neurodegeneration. Thus, the concept of therapeutic administration of human recombinant NGF in AD patients has a strong rationale, being further validated by recent and ongoing clinical trials with a gene-therapy approach. However, the widespread clinical application of gene or cell-therapy strategies for the delivery of NGF to AD patients seems unpractical, and it would be more advantageous to have non-invasive methods, that should also limit the adverse effects of NGF in activating nociceptive responses. This review will describe: 1) the data from preclinical and clinical studies underlying the rationale of NGF as a potential therapeutic agent for AD; and 2) the alternative strategies to reach adequate concentrations of NGF in relevant brain areas while preventing the onset of adverse effects.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / physiology
  • Animals
  • Genetic Therapy
  • Humans
  • Nerve Growth Factors / agonists
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / therapeutic use*
  • Neurodegenerative Diseases / physiopathology
  • Receptors, Nerve Growth Factor / biosynthesis
  • Signal Transduction / drug effects


  • Amyloid beta-Peptides
  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor