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Iwatsubo, Takeshi

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AMYLOID PRECURSOR IN ALZHEIMERS DISEASE

Perry, George

1 April 1988 - 30 June 1995
NATIONAL INSTITUTE ON AGING
Total Funding: $ 536,600

FY 1994
3R01AG007552-06S1
$ 28,992
FY 1993
5R01AG007552-06
$ 135,361
FY 1992
5R01AG007552-05
$ 114,644
FY 1991
2R01AG007552-04
$ 111,949
FY 1990
5R01AG007552-03
$ 45,344
FY 1989
5R01AG007552-02
$ 50,181
FY 1988
1R01AG007552-01
$ 50,129
 
 
$ 536,600
Abstract

(Adapted from the applicant's abstract) 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.

50 Resulting Publications

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