Increase in β-amyloid levels in cerebrospinal fluid of children with down syndrome
Increase in β-amyloid levels in cerebrospinal fluid of children with down syndrome
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DOI：
10.1159/000109215
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发表时间：
2007-01-01
影响因子：
2.4
通讯作者：
Hoglund, Kina
中科院分区：
文献类型：
--
作者：
Englund, Hillevi;Anneren, Goran;Hoglund, Kina
背景：患有唐氏综合症（DS）的人在其一生中总是会患上阿尔茨海默病（AD）。因此，在试图阐明 AD 发病机制的早期事件时，研究年轻的 DS 患者非常重要。目的：研究 DS 儿童脑脊液 (CSF) 中不同淀粉样 β (A beta) 肽以及 tau 蛋白和磷酸化 tau 蛋白的水平如何随时间变化。第一个脑脊液样本是在 8 个月大时采集的，随后的两个样本是在 20-40 个月和 54 个月大时采集的。结果：使用蛋白质印迹法测量时，Aβ 肽的个体水平以及脑脊液中的总 Aβ 水平随着时间的推移而增加。随着时间的推移，脑脊液中的 Tau 蛋白减少，而磷酸化 tau 蛋白的水平没有变化。结论：本研究中观察到的 DS 患者幼儿期脑脊液中 A β 水平升高可能是由于 A β 前体 APP 三体性导致 A β 过量产生。尽管脑脊液中 Aβ 浓度增加，但脑脊液中没有 AD 指示 tau 模式的迹象，因为总 tau 水平下降且磷酸化 tau 保持不变。这一观察结果进一步强化了 AD 中 A beta 病理学先于 tau 病理学的理论。版权所有 (c) 2007 S. Karger AG，巴塞尔。
Background: Individuals with Down syndrome (DS) invariably develop Alzheimer's disease ( AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid-beta (A beta) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20-40 and 54 months of age. Results: Individual levels of the A beta peptides, as well as total A beta levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time. Conclusion: The increasing levels of A beta in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the A beta precursor APP, which leads to an overproduction of A beta. Despite the increased CSF concentrations of A beta, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of A beta pathology preceding tau pathology in AD.Copyright (c) 2007 S. Karger AG, Basel.