Accumulation of beta-amyloid precursor
Accumulation of beta-amyloid precursor
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DOI：
10.1002/ana.410420108
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发表时间：
1997-07-01
影响因子：
11.2
通讯作者：
Scaravilli, F
中科院分区：
文献类型：
--
作者：
Giometto, B;An, SF;Scaravilli, F
人类免疫缺陷病毒1型（HN-B）脑炎患者神经心理异常的发病机制尚不清楚，因为神经元不是感染的目标，并且严重的神经元丢失仅在疾病晚期发生。此外，有证据表明，艾滋病痴呆症是不是一个同质的实体，并可以部分逆转齐多夫定治疗后，发现受损的轴突流，证明β-淀粉样前体蛋白免疫反应性，可能有助于神经心理缺陷，促使本研究。本文研究了完全型获得性免疫缺陷综合征（AIDS）患者的脑，并与正常和异常对照组进行了比较。通过巢式聚合酶链反应研究HIV-1 DNA的存在;通过β-淀粉样前体蛋白、泛素免疫组织化学和银染色检测轴突异常。在所有研究的HIV脑炎脑中均观察到β-淀粉样前体蛋白的积累;免疫染色的外观从球状结构到平行形成的束状结构不等。在2例无病理异常的AIDS脑中，仅检测到后者。创伤后的大脑仅与β-淀粉样前体蛋白抗体发生强烈反应，并且它们内部的不同反应性与创伤后存活率相关，在老年病例中仅检测到球状结构。未发现艾滋病患者中β-淀粉样前体蛋白反应性的不同模式与痴呆之间存在相关性。这些结果表明，广泛的轴突损伤是艾滋病大脑的一个恒定特征，并表明它可能在这些患者的神经心理异常的发病机制中发挥作用。
The pathogenesis of neuropsychological abnormalities in patients with human immunodeficiency virus type 1 (HN-B) encephalitis is obscure because neurons are nor the target of infection and severe neuronal loss occurs only late during the disease. Moreover, there is evidence indicating that HIV dementia is not a homogeneous entity and could partially reverse after treatment with zidovudine, The finding that impaired axonal flow, evidenced by beta-amyloid precursor protein immunoreactivity, could contribute to the neuropsychological deficits prompted the present study. Brains of patients with full-blown acquired immunodeficiency syndrome (AIDS) were studied and findings compared with those of normal and abnormal control subjects. The presence of HIV-1 DNA was investigated by nested polymerase chain reaction; axonal abnormalities were detected by beta-amyloid precursor protein, ubiquitin immunohistochemistry, and silver staining. Accumulation of beta-amyloid precursor protein was observed in all the HIV encephalitis brains studied; the appearance of the immunostaining varied from globular structures to bundles of parallel formations. In 2 AIDS brains without pathological abnormalities, only the latter pattern was detected. The brains with trauma mere strongly reactive with beta-amyloid precursor protein antibody and the different reactivity within them correlated with posttrauma survival, only globular structures being detected in the older cases. No correlation was found between the different pattern of beta-amyloid precursor protein reactivity and dementia in AIDS patients. These results shaw that widespread axonal injury is a constant feature in AIDS brains and suggest that it could play a role in the pathogenesis of the neuropsychological abnormalities of these patients.