Cooley Sarah A, Paul Robert H, Fennema-Notestine Christine, Morgan Erin E, Vaida Florin, Deng Qianqian, Chen Jie Ashley, Letendre Scott, Ellis Ronald, Clifford David B, Marra Christina M, Collier Ann C, Gelman Benjamin B, McArthur Justin C, McCutchan J Allen, Simpson David M, Morgello Susan, Grant Igor, Ances Beau M
University of Missouri - St. Louis, St. Louis, MO, USA.
Missouri Institute of Mental Health, St. Louis, MO, USA.
J Neurovirol. 2016 Oct;22(5):607-614. doi: 10.1007/s13365-016-0434-7. Epub 2016 Mar 28.
Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM), and basal ganglia were examined. Secondary analyses explored this relationship separately in individuals ≥50 years old (n = 173) and <50 years old (n = 63). No significant differences were observed between ApoE ε4+ (ApoE ε3/ε4 and ApoE ε4/ε4) individuals (n = 69) and ApoE ε4- (ApoE ε2/ε3 and ApoE ε3/ε3) individuals (n = 167). When individuals were further divided by age, no significant genotype group differences were identified in individuals <50 or ≥50 years of age on any neuroimaging outcome. The ApoE ε4 allele did not affect brain integrity in this large, diverse sample of HIV+ individuals. The effects of ApoE ε4 may not be apparent until more advanced ages and may be more prominent when present along with other risk factors for neuronal damage.
以往的神经影像学研究表明,在感染人类免疫缺陷病毒(HIV)的个体中,载脂蛋白(ApoE)ε4等位基因与脑完整性之间存在负相关关系,尽管这种关系在整个成年期是否存在尚不清楚。本研究的目的是通过一大群多样化的HIV感染者以及多种对HIV敏感的成像方式来澄清这些差异。在中枢神经系统HIV抗逆转录病毒治疗效果研究(CHARTER)中,对237名HIV感染者的ApoE ε4与结构神经影像学和磁共振波谱(MRS)的关联进行了检查。检查了皮质和皮质下灰质、异常和总白质、脑室、脑沟脑脊液(CSF)以及小脑灰质、白质和CSF体积,以及额叶白质(FWM)、额叶灰质(FGM)和基底神经节中肌醇、肌酸、N-乙酰天门冬氨酸和胆碱的MRS浓度。二次分析分别在年龄≥50岁(n = 173)和<50岁(n = 63)的个体中探讨了这种关系。在携带ApoE ε4(ApoE ε3/ε4和ApoE ε4/ε4)的个体(n = 69)和不携带ApoE ε4(ApoE ε2/ε3和ApoE ε3/ε3)的个体(n = 167)之间未观察到显著差异。当个体按年龄进一步划分时,在年龄<50岁或≥50岁的个体中,在任何神经影像学结果上均未发现显著的基因型组差异。在这个多样化的大样本HIV感染者中,ApoE ε4等位基因不影响脑完整性。ApoE ε4的影响可能直到更年长时才会显现,并且当与其他神经元损伤风险因素同时存在时可能会更显著。