Although with the cloning of the cDNA for the amyloid precursor protein (APP) in late 1986 the sequences and identification of APP have been possible, the importance of APP in the pathogenesis of Alzheimer Disease (AD) is essentially unknown. During the previous funding period, several immunochemical and biochemical probes were produced and used by this laboratory to conclude that neurons are the major source of APP in the senile plaque, the site of the amyloid deposition. They suggest these findings are directly relevant to their original hypothesis: that the intraneuronal cytoskeletal changes of AD, neurofibrillary pathology (NFP), is a direct result of the interaction of APP with the cytoskelton. The finding that NFP contains abundant heparin sulfate proteoglycans (HSPG) gave them a chemical basis for this binding, since APP is an ASPG binding protein. In binding studies, they found that many NFP components specifically associate with APP accumulations. Support was therefore found for the hypothesis that NFP components are incorporated through reciprocal binding. In the present proposal, they will extend these studies through the following aims: (1) Binding studies that will define NFP's biochemistry in situ as well as traditional biochemical properties; (2) determine whether HSPG's are associated with the NFP's of other diseases; (3) determine the relationship of neuritic change to amyloid deposition in AD and control brains; (4) study the effect of APP gradients in the brain through brain implants of APP and B-protein; (5) physical mapping of NFP epitopes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG006159-04A1
Application #
3117004
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1991-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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