Pelech Steven
Professor University of British Columbia, Brain Research Centre and Division of Neurology, Department of Medicine, Vancouver, BC, V6T 2B5, Canada.
Expert Opin Med Diagn. 2008 May;2(5):577-91. doi: 10.1517/17530059.2.5.577.
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.
To investigate the potential of proteomics approaches for AD diagnosis.
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.
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。
研究蛋白质组学方法用于AD诊断的潜力。
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。