A Review of Fluid Biomarkers for Alzheimer's Disease: Moving from CSF to Blood.
A Review of Fluid Biomarkers for Alzheimer's Disease: Moving from CSF to Blood.
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DOI：
10.1007/s40120-017-0073-9
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发表时间：
2017-07
影响因子：
3.7
通讯作者：
Blennow K
中科院分区：
文献类型：
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作者：
Blennow K
阿尔茨海默病（AD）的一组核心脑脊液（CSF）生物标志物包括总tau（T-tau）、磷酸化tau（P-tau）和β-淀粉样蛋白42（Aβ42）。这些生物标志物反映了AD病理生理学的一些关键方面，包括神经元变性、tau磷酸化与缠结形成以及Aβ聚集与肽沉积到斑块中。核心AD CSF生物标志物已经在许多研究中得到临床验证，并且发现在痴呆和疾病的轻度认知障碍阶段两者中具有非常高的诊断性能来识别AD。还发现CSF Aβ42与淀粉样蛋白PET在识别脑淀粉样蛋白沉积方面显示出非常高的一致性。突触蛋白神经颗粒素是AD和前驱AD的新的候选CSF生物标志物。高CSF神经颗粒蛋白预测未来的认知衰退，并且似乎比例如T-tau对AD更特异。重要的是，技术的发展已经提供了超灵敏的测量技术，可以测量血液样本中的tau和神经丝光（NFL）等脑特异性蛋白质。血浆tau和NFL在AD中均增加，最近的研究表明，血浆NFL具有与核心AD CSF生物标志物相当的诊断性能，并预测未来的认知衰退。未来的大型纵向临床研究有必要确定血浆tau和NFL作为初级保健中神经退行性疾病的一线筛查工具的潜力。
A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease. CSF Aβ42 has also been found to show very high concordance with amyloid PET to identify brain amyloid deposition. The synaptic protein neurogranin is a novel candidate CSF biomarker for AD and prodromal AD. High CSF neurogranin predicts future cognitive decline and seems to be more specific for AD than, for example, T-tau. Importantly, technical developments have given ultrasensitive measurement techniques that allow measurement of brain-specific proteins such as tau and neurofilament light (NFL) in blood samples. Both plasma tau and NFL are increased in AD, and a recent study showed that plasma NFL has a diagnostic performance comparable to the core AD CSF biomarkers, and predicted future cognitive decline. Future large longitudinal clinical studies are warranted to determine the potential for plasma tau and NFL to serve as first-in-line screening tools for neurodegeneration in primary care.