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[早老素-1基因E280A突变携带者中β-淀粉样蛋白抗体的检测]

[Detection of antibodies to beta-amyloid in carriers of E280A mutation in the presenilin-1 gene].

作者信息

Toro F, Lopera F, Ossa J, Madrigal L, Mira A, Díaz A, Parra S

机构信息

Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.

出版信息

Rev Neurol. 1999;29(12):1104-7.

PMID:10652730
Abstract

OBJECTIVE

To investigate some immune component that could contribute to the pathogenesis of Alzheimer's disease associated with the E280A mutation of the presenilin-1 gene (PS-1).

PATIENTS AND METHODS

Serum antibodies against both cardiolipin and beta-amyloid peptides (beta 1-40 and beta 1-42) were quantitated by means of an indirect ELISA technique in carriers of the mutation, either healthy or with Alzheimer's disease, as well as in normal controls without the mutation.

RESULTS

Out of 19 patients with Alzheimer's disease only 2 had increased values of antibodies to cardiolipin, namely: one with 14.58 micrograms/ml of IgM and the other with 36.16 micrograms/ml of IgG. The remaining individuals revealed values under 10 micrograms/ml, considered normal, and there was no significant difference between the groups. Significant serum reactivity (p < 0.001) was detected against both beta-amyloid peptides in the mutation carriers, either with or without Alzheimer's disease, as compared to the control group. No correlation was detected between this antibody response and the mental or functional situation of the patients.

CONCLUSION

beta-amyloid antibodies, present in the mutation carriers, may simply represent a marker of immune activation induced by beta-amyloid with no in vivo effect; however, despite the results, the possibility can not be ruled out of a pathogenic role of these antibodies in early onset Alzheimer's disease.

摘要

目的

研究某些可能与早老素 -1基因(PS -1)E280A突变相关的阿尔茨海默病发病机制有关的免疫成分。

患者和方法

采用间接ELISA技术,对携带该突变的健康者或患有阿尔茨海默病者以及无该突变的正常对照者血清中的抗心磷脂抗体和β-淀粉样肽(β1-40和β1-42)抗体进行定量分析。

结果

在19例阿尔茨海默病患者中,只有2例抗心磷脂抗体值升高,即:1例IgM为14.58微克/毫升,另1例IgG为36.16微克/毫升。其余个体的值均低于10微克/毫升,属于正常范围,且各组之间无显著差异。与对照组相比,在携带突变的患者中,无论是否患有阿尔茨海默病,均检测到针对两种β-淀粉样肽的显著血清反应性(p < 0.001)。未检测到这种抗体反应与患者的精神或功能状况之间存在相关性。

结论

突变携带者体内存在的β-淀粉样肽抗体可能仅仅是β-淀粉样肽诱导的免疫激活的标志物,在体内无作用;然而,尽管有这些结果,仍不能排除这些抗体在早发型阿尔茨海默病中具有致病作用的可能性。

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[Detection of antibodies to beta-amyloid in carriers of E280A mutation in the presenilin-1 gene].[早老素-1基因E280A突变携带者中β-淀粉样蛋白抗体的检测]
Rev Neurol. 1999;29(12):1104-7.
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Mean age of onset in familial Alzheimer's disease is determined by amyloid beta 42.家族性阿尔茨海默病的平均发病年龄由β淀粉样蛋白42决定。
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[Image characterization of Alzheimer's disease associated with the E280A-PS1 mutation. Case-control study: MRI findings].
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Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy-terminal fragment.家族性阿尔茨海默病突变抑制γ-分泌酶介导的β-淀粉样前体蛋白羧基末端片段的释放。
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Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for Alzheimer's disease.淀粉样前体蛋白和早老素-1基因的突变会增加小鼠神经细胞的基础氧化应激,并导致对由淀粉样β肽(1-42)、羟基自由基和海藻酸介导的氧化应激敏感性增加:对阿尔茨海默病的启示。
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[Neuropathological findings in early-onset Alzheimer's disease (E280a-PS1 mutation)].
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Alzheimer's disease. Molecular consequences of presenilin-1 mutation.阿尔茨海默病。早老素-1突变的分子后果。
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Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern.在阿尔茨海默病模型中,环氧化酶-2活性以性别二态性模式促进认知缺陷,但不会增加淀粉样蛋白负担。
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[Performance of carriers and non-carriers of the E280A mutation for familial Alzheimer's disease in a naming test].[在命名测试中E280A突变携带者和非携带者对家族性阿尔茨海默病的表现]
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