Department of Geriatric Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Neurobiol Aging. 2012 Apr;33(4):831.e1-9. doi: 10.1016/j.neurobiolaging.2011.07.008. Epub 2011 Aug 31.
Large hour-to-hour variability has previously been demonstrated in the cerebrospinal fluid (CSF) concentrations of Alzheimer's disease (AD) biomarkers amyloid β(42) (Aβ(42)) and Aβ(40) in healthy younger subjects. We investigated the within-subject variability over 36 hours in CSF Aβ and tau proteins, in older subjects and AD patients. Six patients with mild stage AD (59-85 years, Mini Mental State Examination (MMSE) 16-26) and 6 healthy older volunteers (64-77 years) received an intrathecal catheter from which, during 36 hours, each hour 6 mL of CSF was drawn. Concentrations of Aβ(42), Aβ(40), total tau, and phosphorylated tau were determined and the variability was analyzed. Within-subject variability within 3-hour periods was assessed as the coefficient of variation, which was comparable for these 4 biomarkers in controls (4.2%-4.6%) and AD (3.1%-5.8%). Variability over 12 hour periods was 5.3% to 9.5%. These findings suggest that CSF biomarker variability is relatively low in healthy older controls and AD patients. Furthermore, continuous sampling of CSF proved to be a useful and robust method, which may also be used to investigate AD pathogenesis and to evaluate pharmacotherapeutic interventions.
先前的研究已经证明，在健康的年轻受试者的脑脊液（CSF）中，阿尔茨海默病（AD）生物标志物淀粉样蛋白β（42）（Aβ（42））和 Aβ（40）的浓度存在较大的每小时变异性。我们研究了 36 小时内 CSF 中 Aβ 和 tau 蛋白在老年受试者和 AD 患者中的个体内变异性。6 名轻度 AD 患者（59-85 岁，Mini Mental State Examination（MMSE）16-26）和 6 名健康的老年志愿者（64-77 岁）接受了鞘内导管插入术，通过该导管在 36 小时内每小时抽取 6 毫升 CSF。测定了 Aβ（42）、Aβ（40）、总 tau 和磷酸化 tau 的浓度，并分析了变异性。在 3 小时时间段内的个体内变异性作为变异系数进行评估，在对照组（4.2%-4.6%）和 AD 患者（3.1%-5.8%）中，这 4 种生物标志物的变异系数相当。12 小时期间的变异性为 5.3%-9.5%。这些发现表明，CSF 生物标志物的变异性在健康的老年对照组和 AD 患者中相对较低。此外，CSF 的连续采样被证明是一种有用且稳健的方法，也可用于研究 AD 的发病机制和评估药物治疗干预。
