Longitudinal Cerebrospinal Fluid Biomarkers over Four Years in Mild Cognitive Impairment
Longitudinal Cerebrospinal Fluid Biomarkers over Four Years in Mild Cognitive Impairment
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DOI：
10.3233/jad-2012-120019
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Zetterberg, Henrik
中科院分区：
文献类型：
--
作者：
Mattsson, Niklas;Portelius, Erik;Zetterberg, Henrik
脑脊液（CSF）中淀粉样蛋白β（42）（A β（42））、总tau（T-tau）和磷酸化tau（P-tau）的测量可用于预测轻度认知障碍（MCI）患者未来的阿尔茨海默病（AD）痴呆。这些生物标志物与临床进展相关的精确时间发展尚不清楚。早期的研究因随访时间短而受阻。在MCI队列中，我们选择了15名发展为AD（MCI-AD）的患者和15名在4年随访期间保持认知稳定的患者。在三个连续的时间从每个患者的CSF中取样，并分析A β肽、可溶性淀粉样β蛋白前体蛋白片段sA β PP α和sA β PP β、T-tau、P-tau和嗜铬粒蛋白B，其是与调节神经元分泌相关的蛋白质。我们还测量了，第一次在MCI患者，一个扩展面板的A β肽的基质辅助激光解吸/电离飞行时间质谱（MS）。大多数生物标志物在四年内惊人地稳定，变异系数低于或接近10%。然而，MCI-AD患者CSF A β（X-40）和嗜铬粒蛋白B浓度降低，这可能表明随着疾病进展，功能性神经元或突触数量减少。MS A β肽组比任何单一A β肽更有用，以鉴定基线时已存在的MCI-AD患者。了解这些生物标志物及其轨迹可能有助于AD的早期诊断，并可用于未来的临床试验，以跟踪疾病修饰药物的作用。
Cerebrospinal fluid (CSF) measurements of amyloid-beta(42) (A beta(42)), total-tau (T-tau), and phosphorylated tau (P-tau) may be used to predict future Alzheimer's disease (AD) dementia in patients with mild cognitive impairment (MCI). The precise temporal development of these biomarkers in relation to clinical progression is unclear. Earlier studies have been hampered by short follow-up. In an MCI cohort, we selected 15 patients who developed AD (MCI-AD) and 15 who remained cognitively stable during 4 years of follow-up. CSF was sampled at three serial occasions from each patient and analyzed for A beta peptides, the soluble amyloid-beta protein precursor protein fragments sA beta PP alpha and sA beta PP beta, T-tau, P-tau, and chromogranin B, which is a protein linked to regulated neuronal secretion. We also measured, for the first time in MCI patients, an extended panel of A beta peptides by matrix-assisted-laser-desorption/ionization time-of-flight mass spectrometry (MS). Most biomarkers were surprisingly stable over the four years with coefficients of variation below or close to 10%. However, MCI-AD patients decreased in CSF A beta(X-40) and chromogranin B concentrations, which may indicate a reduced number of functional neurons or synapses with disease progression. The MS A beta peptide panel was more useful than any single A beta peptide to identify MCI-AD patients already at baseline. Knowledge on these biomarkers and their trajectories may facilitate early diagnosis of AD and be useful in future clinical trials to track effects of disease modifying drugs.