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CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE

阿尔茨海默病中的脑血管淀粉样蛋白

基本信息

批准号：
2049271
负责人：
GEORGE G GLENNER
金额：
$ 27.64万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-30 至 1998-08-31
项目状态：
已结题

项目摘要

One of the major objectives of the present study is to isolate the putative beta protein precursor(s) from Alzheimer's disease, Down's syndrome and normal sera, cerebrospinal fluid, urine or tissue and to define if chemical differences exist, i.e. an "amyloidogenic" isotype in Alzheimer's disease and Down's syndrome. The identification of such an isotype may lead to a specific diagnostic serum or CSF test for Alzheimer's disease by the use of a radioimmunoassay. Another major objective is to define the proteolytic enzyme characteristics of cerebral vessels that are implicated in the cleavage of beta protein precursor to form amyloid fibrils in cerebral vessel walls and those responsible for its proteolysis to form the amyloid fibrils of "senile" plaques, in order to define proteolytic enzyme differences between cerebral parenchymal cells, e.g. microglia, and endothelial cells, that may explain the differences in vessel and plaque amyloid fibril chemical composition. This study will utilize biochemical procedures extensively for the isolation and characterization of the vascular complement of lysosomal and other proteolytic enzymes. Organotypic endothelial cell cultures will also be employed in this investigation. In the absence of a chemically characterized native amyloid beta protein precursor, the beta protein gene product and its hydrolytic cleavage derivatives will be used as enzyme substrates. The ultimate purpose of this study is to develop reagents selective for the inhibition of cerebral amyloid fibril formation by the prevention of beta protein precursor hydrolysis and, thus, lead to an approach to the therapy of Alzheimer's disease. In addition in vitro radioautographic receptor binding methods will be employed to determine whether the immunohistochemical definition of the beta protein precursor as a receptor-binding protein can be verified. A final objective is to define by chemical, immunochemical and immunohistochemical methods the nature and origin of the paired helical filaments of the neurofibrillary tangles in Alzheimer's disease.

本研究的主要目的之一是分离

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Amyloid beta protein and the basis for Alzheimer's disease.

DOI：
发表时间：
1989
期刊：
Progress in clinical and biological research
影响因子：
0
作者：
G. Glenner
通讯作者：
G. Glenner

The pathobiology of Alzheimer's disease.

DOI：
10.1146/annurev.me.40.020189.000401
发表时间：
1989
期刊：
Annual review of medicine
影响因子：
10.5
作者：
G. Glenner
通讯作者：
G. Glenner

Evidence of amyloid beta-protein immunoreactive early plaque lesions in Down's syndrome brains.

唐氏综合症大脑中淀粉样β蛋白免疫反应性早期斑块病变的证据。

DOI：
发表时间：
1989
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
0
作者：
Ikeda,S;Yanagisawa,N;Allsop,D;Glenner,GG
通讯作者：
Glenner,GG

The proteins and genes of Alzheimer's disease.

阿尔茨海默病的蛋白质和基因。

DOI：
发表时间：
1988
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
0
作者：
Glenner,GG
通讯作者：
Glenner,GG

Collaborative computational anatomy: an MRI morphometry study of the human brain via diffeomorphic metric mapping.

协作计算解剖学：通过微分同态度量映射对人脑进行 MRI 形态测量研究。

DOI：
10.1002/hbm.20655
发表时间：
2009-07
期刊：
HUMAN BRAIN MAPPING
影响因子：
4.8
作者：
Miller, Michael I.;Priebe, Carey E.;Qiu, Anqi;Fischl, Bruce;Kolasny, Anthony;Brown, Timothy;Park, Youngser;Ratnanather, J. Tilak;Busa, Evelina;Jovicich, Jorge;Yu, Peng;Dickerson, Bradford C.;Buckner, Randy L.
通讯作者：
Buckner, Randy L.