Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.
Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.
复制标题
HIV 相关神经认知障碍中磷酸化 tau 蛋白和 IL-8 的脑脊液减少相关。
DOI：
10.1038/s41598-019-45418-2
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发表时间：
2019
影响因子：
4.6
通讯作者：
Hu,WilliamT
中科院分区：
文献类型：
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作者：
Ozturk,Tugba;Kollhoff,Alexander;Anderson,AlbertM;ChristinaHowell,J;Loring,DavidW;Waldrop-Valverde,Drenna;Franklin,Donald;Letendre,Scott;Tyor,WilliamR;Hu,WilliamT
艾滋病毒相关性神经认知障碍(HAND)在发达国家和发展中国家都是一种常见的疾病，但其原因在很大程度上尚不清楚。以前的研究并不一致地将阿尔茨海默病(AD)、病毒负担和炎症与HIV感染者的手部发病联系起来。在这里，我们同时检测了41名接受联合抗逆转录病毒治疗的HIV感染者(14名手部)的脑脊液(CSF)水平、AD已建立的淀粉样蛋白和tau生物标志物、病毒拷贝数和六种关键细胞因子，并将他们的脑脊液模式与年轻健康受试者、认知正常的老年健康受试者和老年AD患者的脑脊液模式进行了比较。在考虑了年龄和种族因素后，HAND与脑脊液中磷酸化tau(p-Tau181)水平最低相关。我们还发现，无论认知程度如何，HIV的脑脊液中都有很高水平的促炎干扰素-γ诱导蛋白10(IP-10/CXCL10)，但脑脊液中的白细胞介素8(IL-8/CXCL8)只在HIV-NC中升高，而在手部则不升高。6个月后，11名HIV感染者接受了重复的脑脊液采集，发现p-Tau181和IL-8水平的纵向变化具有很强的相关性(R = 0.841)。这些数据表明，与IP-10相比，IL-8降低，p-Tau181降低，以表征HAND。
HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer’s disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181to characterize HAND.