Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Neurobiology Department, Hospices Civils de Lyon, Lyon, France; BIORAN team INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, Lyon, France.
Clin Chim Acta. 2015 Sep 20;449:3-8. doi: 10.1016/j.cca.2015.01.041. Epub 2015 Feb 7.
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by neuroaxonal and synaptic degeneration accompanied by intraneuronal neurofibrillary tangles and accumulation of extracellular plaques in specific brain regions. These features are reflected in the AD cerebrospinal fluid (CSF) by increased concentrations of total tau (t-tau) and phosphorylated tau (p-tau), together with decreased concentrations of β-amyloid (Aβ42), respectively. In combination, Aβ42, p-tau and t-tau are 85-95% sensitive and specific for AD in both prodromal and dementia stages of the disease and they are now included in the diagnostic research criteria for AD. However, to fully implement these biomarkers into clinical practice, harmonization of data is needed. This work is ongoing through the standardization of analytical procedures between clinical laboratories and the production of reference materials for CSF Aβ42, p-tau and t-tau. To monitor other aspects of AD neuropathology, e.g., synaptic dysfunction and/or to develop markers of progression, identifying novel candidate biomarkers is of great importance. Based on knowledge from the established biomarkers, exemplified by Aβ and its many variants, and emerging data on neurogranin fragments as biomarker candidate(s), a thorough protein characterization in order to fully understand the diagnostic value of a protein is a suggested approach for successful biomarker discovery.
阿尔茨海默病（AD）是痴呆症最常见的病因，其特征是神经轴突和突触退化，伴随着神经元内神经原纤维缠结和特定脑区细胞外斑块的积累。这些特征在 AD 脑脊液（CSF）中通过总tau（t-tau）和磷酸化 tau（p-tau）浓度的增加，以及β-淀粉样蛋白（Aβ42）浓度的降低来反映。联合 Aβ42、p-tau 和 t-tau 对疾病的前驱期和痴呆期的 AD 具有 85-95%的敏感性和特异性，它们现在已被纳入 AD 的诊断研究标准。然而，为了将这些生物标志物充分应用于临床实践，需要对数据进行协调。这是通过临床实验室之间分析程序的标准化以及 CSF Aβ42、p-tau 和 t-tau 参考物质的生产来进行的。为了监测 AD 神经病理学的其他方面，例如突触功能障碍和/或开发进展标志物，确定新的候选生物标志物非常重要。基于已建立的生物标志物（如 Aβ及其多种变体）的知识，以及神经颗粒蛋白片段作为生物标志物候选物的新兴数据，对蛋白质进行全面的特征分析以充分了解蛋白质的诊断价值是成功发现生物标志物的一种建议方法。
