Olah Zita, Pakaski Magdolna, Janka Zoltan, Kalman Janos
Department of Psychiatry, University of Szeged, Szeged, Hungary.
Neuropsychopharmacol Hung. 2012 Sep;14(3):165-76.
One of the most important neurodegenerative diseases of our time is Alzheimer's disease, which mainly affects the elderly population. The accumulation of β-amyloid and tau protein in the brain tissue is the most characteristic pathomechanical event of the disease, later causing neuronal cell death. Setting up an accurate diagnosis of Alzheimer's disease has essentially changed recently, since besides psychometry, neurochemical and neuroimaging examinations are also gaining greater importance in the clinical routine. Thanks to the widening of diagnostic methods, in the future the disease could be recognised even during the preclinical phase. The most remarkable source of brain-derived compounds is the cerebrospinal fluid. Although obtaining cerebrospinal fluid is greatly unpleasant, it poses a low risk and is frequently used as part of the diagnostic procedure. The assay of cerebrospinal fluid means the identification of the level of β-amyloid(1-42), tau and phospho-tau and their ratio, but to get more specific and sensitive investigations there is intensive research work both on the utility of their combination and on finding even more specific biomarkers. This review gives a summary of the biomarkers that are being used and being researched for the diagnostic tests of both familial and sporadic forms of Alzheimer's disease. Other notable sources of neurochemical compounds are the serum and the plasma, however, the identification of their biomarkers is under preclinical examinations. Unfortunately neither the validation of these markers nor the consistent acceptance of the experimental results is possible due to the wide range of protocols in international research. The importance of biomarkers in the development of potential drug candidates is also discussed.
当今最重要的神经退行性疾病之一是阿尔茨海默病,该病主要影响老年人群。脑组织中β-淀粉样蛋白和tau蛋白的积累是该疾病最典型的病理力学事件,随后会导致神经元细胞死亡。近年来,阿尔茨海默病的准确诊断方法发生了根本性变化,因为除了心理测量外,神经化学和神经影像学检查在临床常规中也变得越来越重要。由于诊断方法的不断拓展,未来甚至在临床前期就能识别出这种疾病。脑源性化合物最显著的来源是脑脊液。尽管获取脑脊液非常令人不适,但它风险较低,且经常作为诊断程序的一部分被使用。脑脊液检测意味着对β-淀粉样蛋白(1-42)、tau蛋白和磷酸化tau蛋白的水平及其比率进行鉴定,但为了获得更特异、更灵敏的检测结果,目前正在对它们的联合应用效用以及寻找更特异的生物标志物进行深入研究。本综述总结了目前正在用于以及正在研究用于家族性和散发性阿尔茨海默病诊断检测的生物标志物。神经化学化合物的其他显著来源是血清和血浆,然而,它们的生物标志物鉴定仍处于临床前研究阶段。不幸的是,由于国际研究中方案的广泛差异,这些标志物的验证以及实验结果的一致认可都无法实现。同时还讨论了生物标志物在潜在候选药物研发中的重要性。