Amyloid β accumulation in axons after traumatic brain injury in humans

Amyloid β accumulation in axons after traumatic brain injury in humans
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DOI:
10.3171/jns.2003.98.5.1072
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发表时间:
2003-05-01
影响因子:
4.1
通讯作者:
Graham, DI
Graham, DI
中科院分区:
医学1区
文献类型:
--
作者:
Smith, DH;Chen, XH;Graham, DI

文献摘要

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目的:尽管在人类创伤性脑损伤(TBI)后不久就发现了由β - 淀粉样蛋白(Aβ)组成的斑块,但这种Aβ的来源尚未确定。在本研究中,作者探讨了受损轴突中Aβ积聚与相关Aβ斑块形成之间的潜在关系。 方法:作者使用对Aβ肽、淀粉样前体蛋白(APP)和神经丝(NF)蛋白具有选择性的抗体,对12例TBI后死亡患者和2例对照患者的石蜡包埋脑切片进行了免疫组织化学分析。在9例脑损伤患者中,在肿胀的轴突中发现了Aβ、APP和NF蛋白的广泛共定位。许多这些免疫反应性轴突轮廓靠近Aβ斑块或被Aβ染色包围,Aβ染色扩散到组织中。在对照患者的大脑中未发现免疫反应性轮廓。 结论:本研究结果表明,受损轴突可作为Aβ的一个大储存库,这可能有助于人类TBI后Aβ斑块的形成。
Object. Although plaques composed of amyloid beta (Abeta) have been found shortly after traumatic brain injury (TBI) in humans, the source for this Abeta has not been identified. In the present study, the authors explored the potential relationship between Abeta accumulation in damaged axons and associated Abeta plaque formation.Methods. The authors performed an immunohistochemical analysis of paraffin-embedded sections of brain from 12 patients who died after TBI and from two control patients by using antibodies selective for Abeta peptides, amyloid precursor protein (APP), and neurofilament (NF) proteins. In nine brain-injured patients, extensive colocalizations of Abeta, APP, and NF protein were found in swollen axons. Many of these immunoreactive axonal profiles were present close to Abeta plaques or were surrounded by Abeta staining, which spread out into the tissue. Immunoreactive profiles were not found in the brains of the control patients.Conclusions. The results of this study indicate that damaged axons can serve as a large reservoir of Abeta, which may contribute to Abeta plaque formation after TBI in humans.