Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS

Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS
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DOI:
10.1097/00005072-199711000-00011
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发表时间:
1997-11-01
影响因子:
3.2
通讯作者:
Scaravilli, F
Scaravilli, F
中科院分区:
医学4区
文献类型:
--
作者:
An, SF;Giometto, B;Scaravilli, F

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神经心理障碍在HIV阳性、症状前个体中的存在是一个有争议的问题。神经影像学研究未显示脑萎缩或白色物质高信号,而质子磁共振波谱显示脑生化异常。使用β-淀粉样前体蛋白(β-APP)的抗体,我们以前证明了艾滋病患者大脑中频繁和广泛的轴突变化。在这项研究中,我们将β-APP的使用扩展到无症状患者,以建立与神经心理障碍可能的形态学相关性。对29名患者的脑样本进行了检查。结果显示8/29例(27%)中β-APP阳性轴突束。在浅表和深部白色物质中观察到的变化为局灶性或弥漫性,无法通过银或泛素染色观察到,并且未与星形胶质细胞和小胶质细胞的分布或形态学变化共存。我们的结论是,在HIV阳性的无症状个体中,轴突变化:(a)可能与免疫激活状态有关,随后在这些患者中观察到毒性物质(包括细胞因子)的存在;(B)可能代表可以进行修复的轻度变化,除非其他病理事件,如AIDS阶段和特定脑炎的发生,使其永久性。
The presence of neuropsychological disturbances in HIV-positive, pre-symptomatic individuals is a controversial issue. Neuroimaging studies have not shown brain atrophy or hyperintensity in the white matter, whereas proton magnetic resonance spectroscopy has revealed some abnormality of cerebral biochemistry. Using an antibody to beta-amyloid precursor protein (beta-APP), we previously demonstrated frequent and widespread axonal changes in the brains of AIDS patients. In this study, we extended the use of beta-APP to asymptomatic patients in order to establish a possible morphological correlation with neuropsychological disorders. Brain samples from 29 patients were examined. Results showed bundles of beta-APP-positive axons in 8/29 cases (27%). The changes, seen in both superficial and deep white matter, were either focal or diffuse, could not be visualized by silver or ubiquitin stains, and did not coexist with any change in distribution or morphology of astrocytes and microglial cells. We conclude that in HIV-positive asymptomatic individuals, axonal changes: (a) may be related to the state of immune activation with consequent presence of toxic substances, including cytokines, observed in these patients; (b) may represent mild changes that could undergo repair, unless other pathological events, such as the supervening of the AIDS stage and the specific encephalitis, make them permanent.