Dupiereux Ingrid, Zorzi Willy, Quadrio Isabelle, Perret-Liaudet Armand, Kovacs Gabor G, Heinen Ernst, Elmoualij Benaïssa
Department of Human Histology-CRPP, University of Liège, Sart Tilman, Belgium.
Cent Nerv Syst Agents Med Chem. 2009 Mar;9(1):2-11. doi: 10.2174/187152409787601950.
Depositions of proteins in form of amyloid and non-amyloid plaques are common pathogenic signs of more than 20 degenerative diseases affecting the central nervous system or a variety of peripheral tissues. Among the neuropathological conditions, Alzheimer's, Parkinson's and the prion diseases, such as Creutzfeldt-Jakob disease (CJD), present ambiguities as regarding their differential diagnosis. At present, their diagnosis must be confirmed by post-mortem examination of the brain. Currently the ante-mortem diagnosis is still based on the integration of multiple data (clinical, paraclinical and biological analyses) because no unique marker exists for such diseases. The detection of specific biomarkers would be useful to develop a differential diagnostic, distinguishing not only different neurodegenerative diseases but also the disease from the non-pathological effects of aging. Several neurodegenerative biomarkers are present at very low levels during the early stages of the disease development and their ultra-low detection is needed for early diagnosis, which should permit more effective therapeutic interventions, before the disease concerned can progress to a stage where considerable damage to the brain has already occurred. In the case of prion diseases, there are concerns regarding not only patient care, but the wider community too, with regard to the risk of transmission of prions, especially during blood transfusion, for which, four cases of variant CJD infection associated with transfusion of non-leukocyte-depleted blood components have been confirmed. Therefore the development of techniques with high sensitivity and specificity represent the major challenge in the field of the protein misfolding diseases. In this paper we review the current analytical and/or biochemical diagnostic technologies used mainly in prion, but also in Alzheimer and Parkinson diseases and emphasizing work on the protein detection as a surrogates and specific biomarker in the body fluid of patients (urine, CSF and blood). This review highlights the urgency of the development of early and sensitive diagnostics in terms of therapeutic challenge.
以淀粉样蛋白和非淀粉样斑块形式存在的蛋白质沉积是影响中枢神经系统或各种外周组织的20多种退行性疾病的常见致病迹象。在神经病理学疾病中，阿尔茨海默病、帕金森病和朊病毒病，如克雅氏病（CJD），在鉴别诊断方面存在模糊性。目前，它们的诊断必须通过大脑的尸检来确认。目前，生前诊断仍基于多种数据（临床、副临床和生物学分析）的整合，因为此类疾病不存在独特的标志物。特异性生物标志物的检测将有助于进行鉴别诊断，不仅能区分不同的神经退行性疾病，还能将疾病与衰老的非病理影响区分开来。几种神经退行性生物标志物在疾病发展的早期阶段含量极低，早期诊断需要对其进行超微量检测，这应能在相关疾病进展到对大脑造成严重损害的阶段之前，实现更有效的治疗干预。对于朊病毒病，不仅涉及患者护理，还关乎更广泛的社区，因为存在朊病毒传播的风险，尤其是在输血过程中，已经证实有4例变异型CJD感染与输注未去除白细胞的血液成分有关。因此，开发具有高灵敏度和特异性的技术是蛋白质错误折叠疾病领域的主要挑战。在本文中，我们综述了目前主要用于朊病毒病，但也用于阿尔茨海默病和帕金森病的分析和/或生化诊断技术，并着重介绍了在患者体液（尿液、脑脊液和血液）中作为替代物和特异性生物标志物的蛋白质检测方面的工作。这篇综述强调了就治疗挑战而言，开发早期和灵敏诊断方法的紧迫性。
