García-Ribas G, López-Sendón Moreno J L, García-Caldentey J
Hospital Ramon y Cajal, Madrid, Espana.
Rev Neurol. 2014 Apr 1;58(7):308-17.
The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.
阿尔茨海默病(AD)的新诊断标准包括脑成像和脑脊液(CSF)生物标志物,目的是提高判断患者是否正在经历AD神经病理过程的确定性。三种CSF生物标志物,即β淀粉样蛋白42(Aβ42)、总tau蛋白和磷酸化tau蛋白,反映了AD的核心病理特征。已知AD的这些病理过程在出现首个症状前数十年就已开始,因此这些生物标志物可能提供疾病早期检测的方法。AD至少可分为三个阶段:临床前AD、AD所致轻度认知障碍以及AD所致痴呆。在本综述中,我们旨在总结每个阶段可用的CSF生物标志物数据。我们还回顾了基于血液的生物标志物的实际研究。近期针对健康老年受试者以及显性遗传性AD突变携带者的研究也发现了生物标志物变化,这些变化能够在这些临床前阶段区分不同组别。这些研究可能有助于在临床试验中对人群进行分层,并客观评估AD病理过程中是否存在变化。除了该过程本身具有侵入性之外,CSF生物标志物广泛应用的局限性还在于各中心之间分析的变异系数较高。这需要严格的分析前和分析程序,这可能使多中心研究以及针对AD不同阶段的全球截断点变得可行。