Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg Mölndal, S-431 80, Mölndal, Sweden.
Mol Neurodegener. 2013 Jun 21;8:20. doi: 10.1186/1750-1326-8-20.
The diagnostic guidelines of Alzheimer's disease (AD) have recently been updated to 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. The CSF biomarkers total tau (T-tau), hyperphosphorylated tau (P-tau) and the 42 amino acid isoform of amyloid β (Aβ42) reflect the core pathologic features of AD, which are neuronal loss, intracellular neurofibrillary tangles and extracellular senile plaques. Since the pathologic processes of AD start decades before the first symptoms, these biomarkers may provide means of early disease detection. The updated guidelines identify three different stages of AD: preclinical AD, mild cognitive impairment (MCI) due to AD and AD with dementia. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review results from blood biomarker studies. In summary, the core AD CSF biomarkers have high diagnostic accuracy both for AD with dementia and to predict incipient AD (MCI due to AD). Longitudinal studies on healthy elderly and recent cross-sectional studies on patients with dominantly inherited AD mutations have also found biomarker changes in cognitively normal at-risk individuals. This will be important if disease-modifying treatment becomes available, given that treatment will probably be most effective early in the disease. An important prerequisite for this is trustworthy analyses. Since measurements vary between studies and laboratories, standardization of analytical as well as pre-analytical procedures will be essential. This process is already initiated. Apart from filling diagnostic roles, biomarkers may also be utilized for prognosis, disease progression, development of new treatments, monitoring treatment effects and for increasing the knowledge about pathologic processes coupled to the disease. Hence, the search for new biomarkers continues. Several candidate biomarkers have been found in CSF, and although biomarkers in blood have been harder to find, some recent studies have presented encouraging results. But before drawing any major conclusions, these results need to be verified in independent studies.
阿尔茨海默病（AD）的诊断指南最近已经更新，纳入了脑成像和脑脊液（CSF）生物标志物，旨在提高患者是否存在持续 AD 神经病理学过程的确定性。CSF 生物标志物总 tau（T-tau）、磷酸化 tau（P-tau）和淀粉样 β 的 42 个氨基酸异构体（Aβ42）反映了 AD 的核心病理特征，即神经元丢失、细胞内神经原纤维缠结和细胞外老年斑。由于 AD 的病理过程在出现首发症状前几十年就已经开始，因此这些生物标志物可能为早期疾病检测提供手段。更新的指南确定了 AD 的三个不同阶段：临床前 AD、AD 所致轻度认知障碍（MCI）和 AD 痴呆。在这篇综述中，我们旨在总结每个阶段的 CSF 生物标志物数据。我们还回顾了血液生物标志物研究的结果。总之，核心 AD CSF 生物标志物对 AD 痴呆和预测早期 AD（AD 所致 MCI）具有较高的诊断准确性。对健康老年人的纵向研究和最近对具有显性遗传 AD 突变的患者的横断面研究也发现了认知正常的高危个体的生物标志物变化。如果疾病修饰治疗成为可能，这将很重要，因为治疗可能在疾病早期最有效。这是一个重要的前提，因为这需要值得信赖的分析。由于测量值在不同的研究和实验室之间存在差异，因此分析前和分析程序的标准化将至关重要。这一过程已经开始。除了发挥诊断作用外，生物标志物还可用于预后、疾病进展、新疗法的开发、治疗效果监测以及增加与疾病相关的病理过程的知识。因此，对新生物标志物的研究仍在继续。已经在 CSF 中发现了一些候选生物标志物，尽管血液中的生物标志物更难发现，但一些最近的研究提出了令人鼓舞的结果。但是，在得出任何主要结论之前，这些结果需要在独立研究中得到验证。
