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:3116392
- 负责人:
- 金额:$ 15.37万
- 依托单位:
- 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 1988-08-31
- 项目状态:已结题
- 来源:
- 关键词:Alzheimer's disease Downs syndrome X ray crystallography amyloidosis biomedical resource blood brain barrier body fluids cerebrovascular disorder diagnosis cerebrovascular system computer data analysis electron microscopy gel electrophoresis high performance liquid chromatography histochemistry /cytochemistry human tissue mental disorder diagnosis monoclonal antibody neurofibrillary tangles postmortem radioimmunoassay
项目摘要
Alzheimer's disease (SDAT) is the fourth most common cause of death in the
U.S. affecting over 2 million people. It represents 60% of all cases of
senile dementia, but no specific diagnostic test for it, short of brain
biopsy, is available to avoid misdiagnosis of treatable dementias. Of SDAT
patients 92% have been found at autopsy to have cerebrovascular amyloidosis
(Congophilic angiopathy). These fibrillar vascular deposits are presumed
to have a deleterious effect by making incompetent the blood-brain
barrier. It is suggested that they may, therfore, be causal in the
pathogenesis of the neurofibrillary tangles and neuritic plaques
characteristic of SDAT. The proposed research is directed at determining
the chemical nature of the cerebrovascular amyloid fibrils in this
condition by isolation, solubilization, fractionation and analytical
methods, e.g. amino acid sequence analysis, previously utilized by the
applicant to define the protein composition of the fibrils in acquired
systemic "primary" amyloidoses. Utilization of these methods should define
the fibril protein chemically, but may not elucidate its origin.
Monoclonal antibodies raised to the fibril protein will be employed in
double immunodiffusion, radioimmunoassay and immunohistochemical techniques
to determine the fibril proteinis/ origin and to quantitate the level of
the protein precursor in tissue and body fluids for potential diagnostic
purposes. These antibodies will also be employed for immunoabsorbant
chromatography to isolate the fibril precursor protein (presumed to be of
serum origin) and to characterize it chemically. These studies will
determine the mechanism of fibril formation, e.g. if a lysosomal defect in
the endothelial processing of the fibril protein precursor causes the
amyloid deposits. Evidence of either a cerebrovascular enzymic defect in
processing of the fibril precursor or the existence of a protein synthetic
abnormality may lead to therapeutic approaches to arrest the course of
SDAT. The recent finding of cerebrovascular amyloidosis, in addition to
plaques and tangles, in 100% of Down's syndrome adults may indicate that
they may be a predictable model for SDAT. Therefore, the above studies
will also be performed on tissues and body fluids from such Down's cases.
The uniqueness of this investigation is that it focuses on the amyloid
angiopathy of SDAT in order to determine the nature of the amyloid fibril
protein and its pathogenesis, but more importantly it has the potential to
define a specific diagnostic serum test for SDAT and to lead directly to an
understanding of its etiology and pathogenesis.
阿尔茨海默病(SDAT)是世界上第四大常见死亡原因
美国影响了200多万人。它占所有病例的60%
老年性痴呆症,但没有专门的诊断测试,缺乏大脑
活检,以避免误诊为可治疗的痴呆。的SDAT
92%的患者在尸检中被发现患有脑血管淀粉样变性
(亲合性血管病)。据推测,这些纤维状血管沉积物
使血脑失灵而产生不良影响
障碍。这表明,它们可能因此在
神经原纤维缠结和神经炎斑块的发病机制
具有SDAT的特点。拟议的研究旨在确定
脑血管淀粉样蛋白纤维的化学性质
通过分离、增溶、分级和分析来获得条件
方法,例如氨基酸序列分析,以前由
申请人确定收购的原纤维的蛋白质组成
全身性“原发”淀粉样变性。这些方法的使用应该定义
原纤维蛋白的化学成分,但可能无法阐明其来源。
针对原纤维蛋白的单抗将用于
双向免疫扩散、放射免疫分析和免疫组织化学技术
确定原纤维蛋白的来源,并定量测定
组织和体液中用于潜在诊断的蛋白质前体
目的。这些抗体也将被用于免疫吸收。
用层析法分离纤维前体蛋白(推测为
血清来源),并对其进行化学表征。这些研究将
确定纤维形成的机制,例如如果溶酶体缺陷
原纤维蛋白前体的内皮加工导致
淀粉样物沉积。脑血管酶缺陷的证据
原纤维前体的加工或蛋白质合成的存在
异常可能导致治疗方法来阻止病程
SDAT。最近发现的脑血管淀粉样变性,除了
100%唐氏综合征成人的斑块和缠结可能表明
它们可能是SDAT的一个可预测的模式。因此,上述研究
也将对唐氏病例的组织和体液进行手术。
这项研究的独特之处在于它关注的是淀粉样蛋白
SDAT血管病变以确定淀粉样原纤维的性质
蛋白质及其发病机制,但更重要的是,它有可能
确定SDAT的特定诊断血清测试,并直接导致
对其病因和发病机制的认识。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('GEORGE G GLENNER', 18)}}的其他基金
PAIRED HELICAL FILAMENT AND PLAQUE AMYLOID PROTEINS
成对的螺旋丝和斑块淀粉样蛋白
- 批准号:
3121258 - 财政年份:1991
- 资助金额:
$ 15.37万 - 项目类别:
PAIRED HELICAL FILAMENTS AND PLAQUE AMYLOID PROTEINS
成对的螺旋丝和斑块淀粉样蛋白
- 批准号:
2050783 - 财政年份:1991
- 资助金额:
$ 15.37万 - 项目类别:
PAIRED HELICAL FILAMENTS AND PLAQUE AMYLOID PROTEINS
成对的螺旋丝和斑块淀粉样蛋白
- 批准号:
3121257 - 财政年份:1991
- 资助金额:
$ 15.37万 - 项目类别:
PAIRED HELICAL FILAMENT AND PLAQUE AMYLOID PROTEINS
成对的螺旋丝和斑块淀粉样蛋白
- 批准号:
3121256 - 财政年份:1991
- 资助金额:
$ 15.37万 - 项目类别:
CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE
阿尔茨海默病中的脑血管淀粉样蛋白
- 批准号:
3480103 - 财政年份:1985
- 资助金额:
$ 15.37万 - 项目类别:
CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE
阿尔茨海默病中的脑血管淀粉样蛋白
- 批准号:
3480104 - 财政年份:1985
- 资助金额:
$ 15.37万 - 项目类别:
CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE
阿尔茨海默病中的脑血管淀粉样蛋白
- 批准号:
2049271 - 财政年份:1985
- 资助金额:
$ 15.37万 - 项目类别:
CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE
阿尔茨海默病中的脑血管淀粉样蛋白
- 批准号:
3116393 - 财政年份:1985
- 资助金额:
$ 15.37万 - 项目类别:
CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE
阿尔茨海默病中的脑血管淀粉样蛋白
- 批准号:
3480100 - 财政年份:1985
- 资助金额:
$ 15.37万 - 项目类别:
CEREBROVASCULAR AMYLOID PROTEIN IN ALZHEIMER'S DISEASE
阿尔茨海默病中的脑血管淀粉样蛋白
- 批准号:
3116390 - 财政年份:1985
- 资助金额:
$ 15.37万 - 项目类别:
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