Project: Research project

Project Details


DESCRIPTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease, affecting memory and cognitive functions. The cholinergic neurons that project into the cerebral cortex and hippocampus are lost in AD. Since acetylcholine transmission is involved with learning and memory, restoration of a cholinergic influence might have therapeutic benefit. Unfortunately, clinical trials using medications to enhance cholinergic function have reported little to no improvement in memory. Failure is likely due to the eventual loss of these neurons. Since survival of cholinergic neurons requires nerve growth factor (NGF) and NGF receptors, NGF-mediated neurotrophic effects may be reduced in AD. TrkA and p75 are receptors on cholinergic neurons that bind to NGF. Activation of TrkA has been linked with cell survival, while activation of p75 may be linked to apoptosis. Abeta accumulates in regions containing cholinergic cell bodies. It is neurotoxic and may interfere with such NGF mediated responses as the regulation of TrkA levels. Increase in p75/TrkA ratio could affect the downstream signaling mechanisms and promote cell death. Alternatively Abeta may interact directly with p75 and activate death signaling mechanisms. I propose to study whether the alterations in the p75/TrkA ratio are involved with he mechanisms that lead to the loss of cholinergic neurons in AD.
Effective start/end date3/1/99 → …


  • National Institutes of Health: $20,575.00
  • National Institute of Mental Health: $20,575.00
  • National Institutes of Health
  • National Institute of Mental Health


  • Medicine(all)


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