Intraneuronal Aβ42 accumulation in Down syndrome brain
Intraneuronal Aβ42 accumulation in Down syndrome brain
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DOI：
10.3109/13506120208995241
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发表时间：
2002-06-01
影响因子：
5.5
通讯作者：
Lemere, CA
中科院分区：
文献类型：
--
作者：
Mori, C;Spooner, ET;Lemere, CA
阿尔茨海默病（AD）大脑显示β（Abeta）斑块、炎症变化和神经元缠结（NFT）。越来越多的证据表明Abeta的神经元起源。对70例3 ~ 73岁唐氏综合征（Down syndrome，DS）患者的颞叶皮质进行了A β N端、A β 40 C端和A β 42 C端的免疫反应性（IR）测定。N-末端抗体未检测到细胞内A β A β 40抗体未检测到显著的细胞内A β，但老年病例在成熟斑块中显示A β 40 IR。相反，Abeta 42抗体显示出明确的神经元内IR。所有Abeta 42抗体测试在非常年轻的DS患者中显示出强烈的神经元内Abeta 42 IR，特别是在所研究的最年轻的病例中（例如，3或4年。老年人），但随着细胞外A，β斑块逐渐积累和成熟，这种IR下降。没有炎症变化与神经元内的Abeta。我们还研究了神经胶质增生和NFT形成的时间发展，揭示了在DS颞叶皮质中，炎症和NFT跟随Abeta沉积。我们的结论是，在唐氏综合征中，Abeta 42在细胞外Abeta沉积之前在细胞内积累，并且随后的细胞外Abeta沉积的成熟引起炎症沉积，引起炎症反应并先于NFT。
Alzheimer's disease (AD) brains display beta (Abeta) plaques, inflammatory changes and neurofibrillary tangles (NFTs). Converging evidence suggests a neuronal origin of Abeta. We performed a temporal study of intraneuronal Abeta accumulation in Down syndrome (DS) brains, Sections from temporal cortex of 70 DS cases aged 3 to 73, years were examined immunohistochemically for immunoreactivity (IR) for the Abeta N-terminal, the Abeta40 C-terminus and the Abeta42 C-terminus. N-terminal antibodies did not detect intracellular Abeta Abeta40 antibodies did not detect significant intracellular Abeta, but older cases showed Abeta40 IR in mature plaques. In contrast, Abeta42 antibodies revealed clear-cut intraneuronal IR. All Abeta42 antibodies test showed strong intraneuronal Abeta42 IR in very young DS patients, especially in the youngest cases studied (e.g., 3 or 4 yr. old), but this IR declined as extracellular A,beta plaques gradually accumulated and matured. No inflammatory changes were associated with intraneuronal Abeta. We also studied the temporal development of gliosis and NFT formation, revealing that in DS temporal cortex, inflammation and NFT follow Abeta deposition. We conclude that Abeta42 accumulates intracellularly prior to extracellular Abeta deposition in Down syndrome, and that subsequent maturation of extracellular Abeta deposits elicits inflammatory deposits elicits inflammatory responses and precedes NFTs.