Neopterin is associated with hippocampal subfield volumes and cognition in HIV.
Neopterin is associated with hippocampal subfield volumes and cognition in HIV.
复制标题
DOI：
10.1212/nxi.0000000000000467
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Barnes LL
中科院分区：
文献类型：
--
作者：
Fleischman DA;Arfanakis K;Leurgans S;Keating SM;Lamar M;Bennett DA;Adeyemi OM;Barnes LL
HIV感染可引发即时免疫反应和炎症性级联反应，导致神经元损伤和认知障碍，但在HIV感染的成年人中，免疫标志物、局部脑体积和认知之间的关系仍未得到充分研究。对66名艾滋病毒感染者、病毒抑制的成年人进行了血清免疫激活标志物(新喋呤)和炎症免疫标志物(白介素[IL]-1β、IL-6、肿瘤坏死因子α和C反应蛋白)与局部脑体积(皮质、皮质下、总灰质、海马体和亚区)和认知之间的横断面相关性研究，这些成年人接受了3.0T核磁共振检查，这是拉什艾滋病毒与老龄化差异卓越中心研究核心的一部分。从冰冻血浆中检测免疫标志物，将值输入线性回归模型作为局部脑体积的预测因子，并检验免疫反应和局部脑体积对认知的交互影响。没有炎性标志物与任何区域脑体积相关。较高的新喋呤水平与较低的海马区、穹隆前区和山角(CA)亚区体积相关。较高的新喋呤水平和较低的海马区总体积独立地与较低的情景记忆相关，并且新喋呤水平完全介导了海马萎缩对情景记忆的影响。较高的新喋呤水平与较低的悬垂前、CA1和CA4/齿状回体积以及较低的语义记忆、工作记忆和全局认知有关。由新喋呤测量的HIV感染后的免疫激活对局部脑结构具有有害的和靶向的影响，这种影响可以通过临床上可用的海马区及其亚区的MRI测量来可视化，并且这种影响与认知功能低下有关。
HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults. Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1β, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined. No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition. Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.