Increased amyloid β protein levels in children and adolescents with Down syndrome
Increased amyloid β protein levels in children and adolescents with Down syndrome
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DOI：
10.1016/j.jns.2006.12.010
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Freedland, Robert L.
中科院分区：
文献类型：
--
作者：
Mehta, Pankaj D.;Capone, George;Freedland, Robert L.
背景：唐氏综合征（DS）患者（40岁及以上）具有阿尔茨海默病（AD）的神经病理学特征。淀粉样蛋白前体蛋白（APP）产生的可溶性淀粉样蛋白β（A β）肽终止于C末端残基40和42。载脂蛋白E（ApoE）β 4等位基因的存在是发生散发性AD的重要危险因素。虽然初步研究表明，血浆A β S2和A β po β 4等位基因与老年痴呆患者DS相关，但尚未研究血浆A 40和A 42水平与DS儿童ApoE表型之间的关系。炎症可能在DS脑的生长中起作用。新蝶呤是一种免疫激活标记物的细胞介导的immune response.Objective：检查血浆A β 40，A β 42，和新蝶呤的水平在儿童或青少年与DS或controls.Materials和方法：血液收集DS（N=35; 7 +/- 3.8岁）和他们的兄弟姐妹（N=34; 10 +/- 4.5）。结果：DS患者血浆A β 40、A β 42水平明显高于正常对照组（P < 0. 05），A β 40、A β 42水平明显高于正常对照组（P < 0. 05）。DS组A β 2/A β 40比值低于对照组。DS组和对照组中年龄与A β 40呈显著负相关，DS组中年龄与A β 42呈显著负相关，而对照组中年龄与A β 42无显著负相关。在两组中，A β 40或A β 42水平与Apo E无相关性。结论：DS患者APP基因过表达导致DS脑内斑块形成前血浆A β 40和A β 42水平升高，而A β 40和A β 42水平与DS和对照组无明显相关性。DS中较高的新蝶呤浓度反映了炎症细胞活化。需要进一步研究以确定血浆A β 42/A β 40比值较低的DS儿童在衰老过程中发生AD的风险是否高于比值较高的儿童。(c)2007 Elsevier B. V.保留所有权利。
Background: Persons with Down syndrome (DS) (40 years and older) have neuropathological changes characteristic of Alzheimer disease (AD). Soluble forms of amyloid beta (A beta) peptide generated from amyloid precursor protein (APP) end at C-terminal residues 40 and 42. The presence of the apolipoprotein E (ApoE) epsilon 4 allele is a significant risk factor for the development of sporadic AD. Although preliminary studies have shown an association of plasma A beta S2 and A beta po epsilon 4 allele in older persons with DS who have dementia, the relationship between plasma A 40 and A 42 levels and ApoE phenotypes in children with DS has not been examined. Inflammation might play a role in the growth of DS brains. Neopterin is an immune activation marker for the cell-mediated immune response.Objective: To examine the levels of plasma A beta 40, A beta 42, and neopterin in children or adolescents with DS or controls.Materials and methods: Blood was collected from DS (N=35; 7 +/- 3.8 years old) and their siblings (N=34; 10 +/- 4.5). Plasma A beta 40 and A beta 42, and neopterin levels were quantitated by sandwich ELISA.Results: A beta 40 and A beta 42 levels were higher in DS than controls. The ratio of A beta 2/A beta 40 was lower in DS than in controls. There were significant negative correlations between age and A beta 40 in DS and controls, and between age and A beta 42 levels in DS but not in controls. There was no association of A beta 40 or A beta 42 levels with Apo E in either group. Neopterin levels were higher in DS than controls, and the levels were not correlated with A beta 40 and A beta 42 levels in DS or controls.Conclusions: The over expression of APP gene in DS leads to increases in plasma A beta 40 and A beta 42 levels before plaque formation in DS brain. Higher neopterin concentrations in DS reflect inflammatory cell activation. Further studies are needed to determine whether DS children with lower plasma A beta 42/A beta 40 ratios are at increased risk of developing AD during aging than those with higher ratios. (c) 2007 Elsevier B.V. All rights reserved.