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Neurotrophic factors and Alzheimer’s disease: are we focusing on the wrong molecule?

  • M. Fahnestock
  • D. Garzon
  • R. M. D. Holsinger
  • B. Michalski
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 62)

Abstract

Brain derived neurotrophic factor (BDNF) promotes cholinergic neuron function and survival. In Alzheimer’s disease, BDNF mRNA and protein are decreased in basal forebrain cholinergic neuron target tissues such as cortex and hippocampus. Using RT-PCR, we demonstrate that BDNF is synthesized in basal forebrain, supplying cholinergic neurons with a local as well as a target-derived source of this factor. BDNF mRNA levels are decreased 50% in nucleus basalis of Alzheimer disease patients compared to controls. Thus, not only do the basal forebrain cholinergic neurons have a reduced supply of target-derived BDNF, but also of local BDNF. We also show by Western blotting that human CNS tissue contains both proBDNF and mature BDNF protein. Moreover, we demonstrate a significant (2.25-fold) deficit in proBDNF protein in Alzheimer’s disease parietal cortex compared to controls. Thus, reduced BDNF mRNA and protein levels in Alzheimer’s disease suggests that BDNF administration may be an effective therapeutic strategy for this disorder.

Keywords

Nerve Growth Factor Brain Derive Neurotrophic Factor Basal Forebrain Nucleus Basalis Basal Forebrain Cholinergic Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • M. Fahnestock
    • 1
  • D. Garzon
    • 1
  • R. M. D. Holsinger
    • 1
  • B. Michalski
    • 1
  1. 1.Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada

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