Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 5541, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 5541, USA; Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
EBioMedicine. 2018 Mar;29:31-37. doi: 10.1016/j.ebiom.2018.02.005. Epub 2018 Feb 8.
BACKGROUND: Reduction of brain volume (brain atrophy) during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the Human Leukocyte Antigen (HLA) allele DRB113:02 which prevents brain atrophy in Gulf War Illness (James et al., 2017). METHODS: Seventy-one cognitively healthy women (32-69years old) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB113:02 allele (No DRB113:02 group, N=60) or carried the DRB113:02 allele (N=11). We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume) was the dependent variable and age was the independent variable. FINDINGS: In the No DRB113:02 group, the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter were reduced highly significantly. In contrast, none of these volumes showed a statistically significant reduction with age in the DRB113:02 group. INTERPRETATION: These findings document the protective effect of DRB113:02 on age-dependent reduction of brain gray matter in healthy individuals. Since the role of this allele is to connect to matching epitopes of external antigens for the subsequent production of antibodies and elimination of the offending antigen, we hypothesize that its protective effect may be due to the successful elimination of such antigens to which we are exposed during the lifespan, antigens that otherwise would persist causing gradual brain atrophy. In addition, we consider a possible beneficial role of DRB113:02 attributed to its binding to cathepsin S, a known harmful substance in brain aging (Wendt et al., 2008). Of course, other factors covarying with the presence of DRB1*13:02 could be involved.
背景：健康大脑衰老过程中脑容量减少（脑萎缩）已有充分记录，并且受遗传、生活方式和环境因素影响。在这里，我们研究了在没有人类白细胞抗原（HLA）等位基因 DRB1*13:02 的情况下脑灰质体积减少的可能性，该等位基因可预防海湾战争病中的脑萎缩（James 等人，2017 年）。
方法：71 名认知健康的女性（32-69 岁）接受了结构磁共振成像（sMRI）扫描，以测量总灰质、皮质灰质和皮质下灰质的体积。参与者根据是否缺乏 DRB113:02 等位基因（无 DRB113:02 组，N=60）或携带 DRB1*13:02 等位基因（N=11）分为两组。我们通过执行线性回归来评估每组脑灰质体积随年龄的变化，其中脑体积（调整为总颅内体积）为因变量，年龄为自变量。
结果：在无 DRB113:02 组中，总灰质、皮质灰质和皮质下灰质体积显著减少。相比之下，在 DRB113:02 组中，这些体积均未显示出与年龄相关的统计学显著减少。
解释：这些发现记录了 DRB113:02 对健康个体中脑灰质与年龄相关减少的保护作用。由于该等位基因的作用是连接外部抗原的匹配表位，以便随后产生抗体并消除致病抗原，我们假设其保护作用可能是由于成功消除了我们在整个生命周期中接触到的此类抗原，否则这些抗原会持续存在导致逐渐的脑萎缩。此外，我们考虑了 DRB113:02 与组织蛋白酶 S 结合的可能有益作用，组织蛋白酶 S 是脑衰老过程中的一种已知有害物质（Wendt 等人，2008 年）。当然，可能还有其他与 DRB1*13:02 共存的因素。
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