Cholinergic neurons within the basal forebrain containing receptors for nerve growth factor. Multiple converging lines of evidence have demonstrated that basal forebrain neurons consistently degenerate in Alzheimer's disease. The resulting cholinergic deficit in cortex occurs early in the disease process and highly correlates with the severity and duration of Alzheimer's disease. This has led to the hypothesis that impaired trophic support by nerve growth factor leads to the degeneration seen in this important region. To date, there is no direct evidence to support this contention although we have argued that this hypothesis had been poorly investigated and results to the contrary are based upon limited and potentially misinterpreted data. We have recently observed that the cholinergic septohippocampal system, in contrast to the cortical and amygdaloid projecting neurons within the nucleus basalis,is not impaired in Alzheimer's disease. We contend that the preservation of these neurons may be due to the fact that the hippocampus contains three times as much nerve growth factor, should degenerate if nerve growth factor is indeed rescuing the cholinergic neurons in this disease. Furthermore, correlations between basal forebrain degeneration (cholinergic and noncholinergic) will be made with cortical pathology in early diagnosed cases of Alzheimer's disease which have come to post-mortem. Finally, the status of nerve growth factor receptors in Alzheimer's disease will be assessed via a quantitative immunoautoradiographic procedure. These data will determine whether there is a reduction of nerve growth factor receptors per basal forebrain neuron in Alzheimer's disease thus precipitating degeneration within these cells. Alternatively, no change or receptor up-regulation would indicate that these neurons would be capable of responding to nerve growth factor therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG009466-04
Application #
3746072
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612
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