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用于阿尔茨海默病诊断的生物标志物鉴定

Biomarker identification for diagnosis of Alzheimer's disease.

作者信息

Pelech Steven

机构信息

Professor University of British Columbia, Brain Research Centre and Division of Neurology, Department of Medicine, Vancouver, BC, V6T 2B5, Canada.

出版信息

Expert Opin Med Diagn. 2008 May;2(5):577-91. doi: 10.1517/17530059.2.5.577.

DOI:10.1517/17530059.2.5.577
PMID:23495745
Abstract

BACKGROUND

Alzheimer's disease (AD) is one of the most pressing and difficult to diagnose unmet diseases confronting industrialized countries. It is characterized by the appearance in the post mortem autopsied AD brain of amyloid plaques containing Aβ42 and paired helical filaments in neurofibrillary tangles with hyperphosphorylated tau.

OBJECTIVE

To investigate the potential of proteomics approaches for AD diagnosis.

METHODS

This reviews focuses on studies of the altered phosphorylation of tau and other proteins as detected in brain biopsy, cerebral spinal fluid (CSF) and blood samples.

RESULTS/CONCLUSION: Detection of decreased Aβ42, and increased total and hyperphosphorylated tau in CSF from AD patients can provide a fairly reliable diagnosis. Furthermore, very recent studies have demonstrated altered levels of cytokines in plasma and differential gene expression and protein phosphorylation in peripheral blood mononuclear cells from AD patients. Identification of the roles of these proteins may provide valuable insights into the underlying molecular pathology of AD and possible sites for therapeutic intervention.

摘要

背景

阿尔茨海默病(AD)是工业化国家面临的最紧迫且最难诊断的未满足需求的疾病之一。其特征是在死后尸检的AD大脑中出现含有Aβ42的淀粉样斑块以及神经原纤维缠结中高度磷酸化tau的双螺旋丝。

目的

研究蛋白质组学方法用于AD诊断的潜力。

方法

本综述聚焦于在脑活检、脑脊液(CSF)和血液样本中检测到的tau及其他蛋白质磷酸化改变的研究。

结果/结论:检测AD患者脑脊液中Aβ42减少以及总tau和高度磷酸化tau增加可提供相当可靠的诊断。此外,最近的研究表明AD患者血浆中细胞因子水平改变,外周血单核细胞中基因表达差异和蛋白质磷酸化也有变化。确定这些蛋白质的作用可能为AD潜在的分子病理学及可能的治疗干预位点提供有价值的见解。

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Biomarker identification for diagnosis of Alzheimer's disease.用于阿尔茨海默病诊断的生物标志物鉴定
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Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain.脑脊液β淀粉样蛋白42和tau蛋白作为大脑中阿尔茨海默病型病理变化的生物标志物。
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Unique Alzheimer's disease paired helical filament specific epitopes involve double phosphorylation at specific sites.独特的阿尔茨海默病双螺旋丝特异性表位涉及特定位点的双重磷酸化。
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MRI and CSF studies in the early diagnosis of Alzheimer's disease.磁共振成像(MRI)和脑脊液研究在阿尔茨海默病早期诊断中的应用
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Regions with abundant neurofibrillary pathology in human brain exhibit a selective reduction in levels of binding-competent tau and accumulation of abnormal tau-isoforms (A68 proteins).人类大脑中神经原纤维病变丰富的区域,其具有结合能力的tau蛋白水平会选择性降低,且异常tau异构体(A68蛋白)会积累。
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Amyloid pathology influences aβ1-42 cerebrospinal fluid levels in dementia with lewy bodies.淀粉样蛋白病理影响路易体痴呆患者的脑脊液 Aβ1-42 水平。
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CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease.脑脊液磷酸化tau蛋白与阿尔茨海默病的新皮质神经原纤维病理改变相关。
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引用本文的文献

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Exp Gerontol. 2014 Feb;50:114-21. doi: 10.1016/j.exger.2013.12.001. Epub 2013 Dec 10.
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Platelet-derived secreted amyloid-precursor protein-β as a marker for diagnosing Alzheimer's disease.血小板衍生的分泌淀粉样前体蛋白-β作为诊断阿尔茨海默病的标志物。
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