Measurement of α- and β-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
Measurement of α- and β-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
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DOI：
10.1016/s0014-4886(03)00027-x
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发表时间：
2003-09-01
影响因子：
5.3
通讯作者：
Blennow, K
中科院分区：
文献类型：
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作者：
Olsson, A;Höglund, K;Blennow, K
阿尔茨海默病（AD）的主要组织病理学标志之一是主要由β-淀粉样蛋白（Abeta）聚集物组成的多余老年斑。淀粉样前体蛋白 (APP) 的选择性裂解发生在正常人和 AD 受试者中，导致可溶性 APP (sAPP) 和 Abeta 的产生和分泌。我们使用新开发的夹心酶联免疫吸附测定方法，检测了 81 名散发性 AD 患者、19 名轻度认知障碍患者和 42 名健康对照者的脑脊液 (CSF) 中的 α 和 β 分泌酶裂解的 sAPP（α-sAPP 和 β-sAPP）。我们发现散发性 AD 患者和健康对照之间的 CSF-α-sAPP 和 CSF-β-sAPP 水平均无差异。这些发现进一步支持了散发性 AD 中 APP 表达没有变化的结论。然而，与对照组相比，轻度认知障碍患者的 CSF-β-sAPP 水平显着升高。我们还研究了 Alphabeta-sAPP 和 Abeta(42) 的 CSF 水平与 apoE epsilon4 (apoFA.) 等位基因之间的关系。具有一或两个 apoE4 等位基因的 AD 患者中的 CSF-α-sAPP 水平显着低于不具有 apoE4 等位基因的患者。比较 ApoE4 等位基因阳性和等位基因阴性个体时，CSF-beta-sAPP 和 CSF-Abeta(42) 的水平均无差异。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.