When cultured with senile plaques obtained at autopsy from individuals with AD, microglia release a potent neurotoxic factor. The present proposal is designed to identify the stimulus for the production of this microglial factor by determining the specific sequence(s) within the beta-amyloid peptide responsible for microglial attachment and activation of neurotoxic activity. Preliminary data is presented demonstrating that, in vitro, microglia adhere to beta-amyloid and are stimulated to initiate an immunologic cascade which results in neuronal injury. A number of approaches to interrupt this cascade and prevent the production of this neurotoxin are proposed, with the long-term goal of preventing neural loss in AD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS034110-02
Application #
2519972
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Oliver, Eugene J
Project Start
1996-09-01
Project End
2001-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030