Immune complexes of auto-antibodies against Aβ1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients
Immune complexes of auto-antibodies against Aβ1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients
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DOI：
10.1038/sj.mp.4001947
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发表时间：
2007-06-01
影响因子：
11
通讯作者：
Wiltfang, J.
中科院分区：
文献类型：
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作者：
Henkel, A. W.;Dittrich, P. S.;Wiltfang, J.
评估了阿尔茨海默氏痴呆（AD）患者和非AD对照（nAD）脑脊液（CSF）中大A β肽结合颗粒（LAPs）的诊断潜力。两组共聚焦光谱均检测到lap，个体间差异较大。共聚焦显微镜分子成像显示lap是异质超聚集体，可在形态上细分为四种主要类型（LAP1-4）。LAP-4型，类似于“大珍珠链”，在42.1%的nAD对照组中检测到，但在AD患者中几乎不存在。LAP-4型可以被蛋白A珠选择性去除，这清楚地表明它除了含有β -淀粉样蛋白肽外还含有免疫球蛋白（A β 1-42）。我们观察到lap与对照组脑脊液中免疫球蛋白G （IgG）浓度密切相关，而与AD患者无关。用抗A β抗体和抗IgG抗体对LAP-4型进行双重标记，证实LAP-4型由A β和IgG聚集物组成。我们的研究结果表明，通过在免疫复合物中聚集这种肽，免疫系统在调节a β 1-42稳态中发挥了核心作用。
The diagnostic potential of large A beta-peptide binding particles (LAPs) in the cerebrospinal fluid (CSF) of Alzheimer's dementia (AD) patients and non-AD controls (nAD) was evaluated. LAPs were detected by confocal spectroscopy in both groups with high inter-individual variation in number. Molecular imaging by confocal microscopy revealed that LAPs are heterogeneous superaggregates that could be subdivided morphologically into four main types (LAP1-4). LAP-4 type, resembling a 'large chain of pearls', was detected in 42.1% of all nAD controls but it was virtually absent in AD patients. LAP-4 type could be selectively removed by protein A beads, a clear indication that it contained immunoglobulins in addition to beta-amyloid peptides (A beta 1-42). We observed a close correlation between LAPs and immunoglobulin G (IgG) concentration in CSF in controls but not in AD patients. Double labeling of LAPs with anti-A beta and anti-IgG antibodies confirmed that LAP-4 type consisted of A beta and IgG aggregates. Our results assign a central role to the immune system in regulating A beta 1-42 homeostasis by clustering this peptide in immunocomplexes.