Accumulation of β‐amyloid precursor protein in HIV encephalitis: Relationship with neuropsychological abnormalities

Accumulation of β‐amyloid precursor protein in HIV encephalitis: Relationship with neuropsychological abnormalities
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HIV 脑炎中β-淀粉样前体蛋白的积累:与神经心理异常的关系

DOI:
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发表时间:
1997
期刊:
影响因子:
--
通讯作者:
F. Scaravilli
F. Scaravilli
中科院分区:
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文献类型:
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作者:
B. Giometto;S. An;M. Groves;T. Scaravilli;J. Geddes;Robert Miller;B. Tavolato;Andrew A. J. Beckett;F. Scaravilli

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人类免疫缺陷病毒1型(HIV-1)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,严重的神经元丢失仅在疾病后期发生。此外,有证据表明,艾滋病毒痴呆症不是一个同质的实体,可以部分逆转后,与齐多夫定治疗。β-淀粉样前体蛋白免疫反应性证明受损的轴突流动可能导致神经心理学缺陷,这一发现促使了本研究。研究了患有全面获得性免疫缺陷综合征(AIDS)的患者的大脑,并将结果与正常和异常对照受试者的结果进行了比较。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聚;免疫染色的外观从球状结构到平行形成的束变化。在2例无病理异常的AIDS脑中,仅检测到后者。创伤后的大脑与β-淀粉样前体蛋白抗体有强烈的反应性,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。在艾滋病患者中,β-淀粉样前体蛋白反应性的不同模式与痴呆之间没有发现相关性。这些结果表明,广泛的轴突损伤是一个恒定的功能,在艾滋病的大脑,并建议它可以发挥作用的发病机制,这些患者的神经心理异常。
The pathogenesis of neuropsychological abnormalities in patients with human immunodeficiency virus type 1 (HIV‐1) encephalitis is obscure because neurons are not 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 β‐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 β‐amyloid precursor protein, ubiquitin immunohistochemistry, and silver staining. Accumulation of β‐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 were strongly reactive with β‐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 β‐amyloid precursor protein reactivity and dementia in AIDS patients. These results show 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.
DOI: 10.1080/01947648809513542
发表时间: 1988-12
期刊: The Journal of legal medicine
影响因子: --
作者:
L. Prockop
通讯作者: L. Prockop
DOI: 10.1073/pnas.87.4.1561
发表时间: 1990-02-01
影响因子: 11.1
作者:
KOO, EH;SISODIA, SS;PRICE, DL
通讯作者: PRICE, DL
DOI: 10.1126/science.1439760
发表时间: 1992-10-02
期刊: SCIENCE
影响因子: 56.9
作者:
SHOJI, M;GOLDE, TE;YOUNKIN, SG
通讯作者: YOUNKIN, SG