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首页> 外文期刊>Archives of general psychiatry. >Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.
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Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.

机译：协会的等离子体clusterin浓度严重程度、病理和老年痴呆症的恶化疾病。

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CONTEXT: Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD). OBJECTIVE: To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach. DESIGN: Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model. SETTING: A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging. PARTICIPANTS: Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging. MAIN OUTCOME MEASURES: Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid. RESULTS: Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques. CONCLUSIONS: These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.
机译：背景:Blood-based分析物可能的指标阿尔茨海默病(AD)的病理过程。目的:确定等离子体相关的蛋白质广告使用结合蛋白质组学和病理学神经影像学方法。蛋白质组学确定等离子体相关的蛋白质病理学的相关广告。验证中使用immunodetection复制设置和动物模型。欧洲研究(AddNeuroMed)和巴尔的摩衰老的纵向研究。广告,患者与轻度认知对象障碍,与健康对照组标准化的临床评估和结构神经影像。血浆蛋白与脑萎缩的疾病严重程度和临床进展率。扩展研究在人类和转基因小鼠检测血浆蛋白之间的关系和大脑淀粉样蛋白。Clusterin / J与载脂蛋白内嗅皮层萎缩,基线疾病严重程度和临床进展迅速在广告。clusterin预测更大的纤维淀粉样β蛋白在内侧颞叶的负担。广告增加了clusterin主题信使RNA在血,但没有效果单核苷酸多态性的基因编码clusterin与基因或蛋白质表达式。增加等离子体凝聚素年龄相关性增加大脑凝聚素以及淀粉样蛋白和clusterin colocalization斑块。结论:这些结果表明一个clusterin重要作用的发病机理的广告,表明淀粉样改变伴护蛋白质可能是生物相关外围签名的广告。

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