Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil.
Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil.
J Neurovirol. 2018 Feb;24(1):28-40. doi: 10.1007/s13365-017-0591-3. Epub 2017 Oct 23.
Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aβ) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and β (sAPPα, sAPPβ), Aβ oligomers 38, 40, 42, and Aβ-total; phosphorylated tau (P-tau), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p values were corrected for multiple testing with the Benjamini-Hochberg procedure. CSF Aβ-42 and Hulstaert (P-tau) index were lower in HIV1-C than B (p = 0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau (p < 0.001), and sAPPα (p = 0.041); HIV(+) had higher CSF Aβ-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau/Aβ-42, T-tau/Aβ-42, P-tau/T-tau, sAPPα/β (all p ≤ 0.01) than AD. Compared to HIV(-), HIV(+) had lower CSF Aβ-42, and T-tau (all p ≤ 0.004). As conclusion, amyloid metabolism was influenced by HIV infection in a subtype-dependent manner. Aß-42 levels were lower in HIV1-C than B, suggesting that there may be greater deposition of Aß-42 in HIV1-C. These findings are supported by CSF Hulstaert (P-tau) index. Differences between HIV and AD in the patterns of Aß and Tau biomarkers suggest that CNS HIV infection and AD may not share some of same mechanisms of neuronal injury.
基于先前的研究表明 HIV-1 Tat 蛋白调节淀粉样β（Aβ）代谢，本研究旨在比较 27 例 HIV 亚型 B 患者、26 例 HIV 亚型 C 患者、18 例健康 HIV 阴性对照者和 24 例阿尔茨海默病（AD）患者的 CSF 神经损伤生物标志物。采用免疫分析法测定可溶性淀粉样前体蛋白α和β（sAPPα、sAPPβ）、Aβ 寡聚物 38、40、42 和 Aβ 总量；磷酸化 tau（P-tau）和总 tau（T-tau）。对 HIV（+）和 HIV（-）（包括 AD）与性别和年龄进行线性回归调整；对 HIV 亚型比较进行了最小 CD4 和血浆病毒载量抑制的调整。采用 Benjamini-Hochberg 程序对多重检验进行校正，比较 HIV1-C 和 B 之间的 CSF Aβ-42 和 Hulstaert（P-tau）指数（p=0.03 和 0.049）；在其他 CSF 生物标志物或比值方面，亚型之间无差异。与 AD 相比，HIV（+）患者 CSF 中的 T-tau、P-tau（p<0.001）和 sAPPα 水平较低（p=0.041）；HIV（+）患者的 CSF Aβ-42 水平较高（p=0.002），CSF 指数也较高：[Aß-42/（240+1.18T-tau）]、P-tau/Aβ-42、T-tau/Aβ-42、P-tau/T-tau、sAPPα/β（所有 p 值均≤0.01）高于 AD。与 HIV（-）相比，HIV（+）患者的 CSF Aβ-42 和 T-tau 水平较低（均 p≤0.004）。结论：淀粉样代谢受 HIV 感染的影响，且具有亚型依赖性。与 HIV 亚型 B 相比，HIV 亚型 C 的 CSF Aβ-42 水平较低，提示 HIV 亚型 C 中可能有更多的 Aβ-42 沉积。这些发现得到了 CSF Hulstaert（P-tau）指数的支持。HIV 与 AD 在 Aβ 和 Tau 生物标志物模式方面的差异表明，中枢神经系统 HIV 感染和 AD 可能没有一些相同的神经元损伤机制。
