Role of HIV in amyloid metabolism.

Role of HIV in amyloid metabolism.
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DOI:
10.1007/s11481-014-9546-0
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发表时间:
2014-09
影响因子:
6.2
通讯作者:
Ances, Beau M.
Ances, Beau M.
中科院分区:
医学3区
文献类型:
--
作者:
Ortega, Mario;Ances, Beau M.

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由于联合抗逆转录病毒治疗 (cART),HIV 感染已从一种急性破坏性疾病转变为一种更为慢性的疾病。在 cART 时代,HIV 感染者 (HIV+) 的预期寿命有所增加。更多 HIV+ 个体正在老龄化,目前预测表明,到 2015 年,50% 的 HIV+ 个体将超过 50 岁。随着年龄的增长,HIV+ 个体患其他潜在神经退行性疾病 [特别是阿尔茨海默病 (AD)] 的风险可能会增加。病理学研究表明,HIV 会增加细胞内和可能细胞外的淀粉样蛋白 β (Aβ42),这是 AD 的一个标志。我们回顾了Aβ42的合成和清除以及HIV对淀粉样蛋白途径的影响,并对比了AD和HIV对Aβ42代谢的影响。 HIV+ 的生物标志物研究(脑脊液 AB 和淀粉样蛋白成像)显示出不同的结果。已证明,在患有 HIV 相关神经认知障碍 (HAND) 的 HIV+ 患者中,CSF Aβ42 正常或减弱。使用 [11C] PiB 进行淀粉样蛋白成像也未证明 HAND 患者细胞外淀粉样纤维沉积增加。我们使用 [11C] PiB 淀粉样蛋白成像进一步证明,老年 HIV+ 患者中 Aβ42 沉积并未增加。总之,这些结果表明 HIV 和衰老各自独立地影响 Aβ42 沉积,不存在显着的相互作用。老年 HIV 阳性患者患 AD 的风险可能不会增加。然而,未来使用多种方式(包括脑脊液标记物和淀粉样蛋白成像相结合)对老年 HIV+ 患者进行纵向研究对于研究 HIV 对 Aβ42 代谢的影响是必要的。
HIV infection has changed from an acute devastating disease to a more chronic illness due to combination anti-retroviral treatment (cART). In the cART era, the life expectancy of HIV-infected (HIV+) individuals has increased. More HIV+ individuals are aging with current projections suggesting that 50% of HIV+ individuals will be over 50 years old by 2015. With advancing age, HIV+ individuals may be at increased risk of developing other potential neurodegenerative disorders [especially Alzheimer’s disease (AD)]. Pathology studies have shown that HIV increases intra and possibly extracellular amyloid beta (Aβ42), a hallmark of AD. We review the synthesis and clearance of Aβ42 and the effects of HIV on the amyloid pathway, and contrast the impact of AD and HIV on Aβ42 metabolism. Biomarker studies (cerebrospinal fluid AB and amyloid imaging) in HIV+ have shown mixed results. CSF Aβ42 has been shown to be either normal or diminished in HIV+ patients with HIV associated neurocognitive disorders (HAND). Amyloid imaging using [11C] PiB has also not demonstrated increased extracellular amyloid fibrillar deposits in HAND patients. We further demonstrate that Aβ42 deposition is not increased in older HIV+ patients using [11C] PiB amyloid imaging. Together, these results suggest that HIV and aging each independently affect Aβ42 deposition with no significant interaction present. Older HIV+ patients are probably not at increased risk for developing AD. However, future longitudinal studies of older HIV+ patients using multiple modalities (including the combination of CSF markers and amyloid imaging) are necessary for investigating the effects of HIV on Aβ42 metabolism.
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