IRCCS, Don Gnocchi Foundation , Milan , Italy.
Front Aging Neurosci. 2013 Nov 25;5:81. doi: 10.3389/fnagi.2013.00081. eCollection 2013.
Neuroinflammation and brain functional disconnection result from β-amyloid (Aβ) accumulation and play fundamental roles in the pathogenesis of Alzheimer's disease (AD). We investigated possible correlations between these two AD-associated phenomena using DTI-based tractography and immunologic analyses in people with amnestic mild cognitive impairment (aMCI) and AD. DTI-Analyses focused on corpus callosum (CC). We found that frontal CC regions were preserved with respect to the posterior ones in aMCI; in these individuals significant correlations were seen between DTI-derived metrics in frontal-parietal CC areas and Aβ42-stimulated BDNF-producing CD4+ T lymphocytes and PDL-1-expressing CD14+ cells. These associations were lost in AD where DTI data involving the same CC areas correlated instead with Aβ42-stimulated interleukin (IL)-21 producing CD4+ T lymphocytes. Higher susceptibility to PDL-1-mediated apoptosis of Aβ42-specific lymphocytes and BDNF-associated survival of existing neurons could contribute to the relative CC structure preservation seen in aMCI. These potentially protective mechanisms are lost in frank AD, when severe alterations in the CC are mirrored in peripheral blood by proinflammatory cytokines-producing T cells. Monitoring of immune cells in peripheral blood could have a prognostic value in AD.
神经炎症和大脑功能连接中断是由β-淀粉样蛋白（Aβ）积累引起的，在阿尔茨海默病（AD）的发病机制中起着至关重要的作用。我们使用基于 DTI 的束追踪和免疫分析研究了这两种与 AD 相关现象之间的可能相关性，研究对象为遗忘型轻度认知障碍（aMCI）和 AD 患者。DTI 分析集中在胼胝体（CC）上。我们发现，在 aMCI 中，额叶 CC 区域相对于后部 CC 区域得以保留；在这些个体中，额叶-顶叶 CC 区域的 DTI 衍生指标与 Aβ42 刺激产生脑源性神经营养因子的 CD4+T 淋巴细胞和表达 PDL-1 的 CD14+细胞之间存在显著相关性。这些相关性在 AD 中消失了，AD 中同一 CC 区域的 DTI 数据与 Aβ42 刺激产生白细胞介素（IL）-21 的 CD4+T 淋巴细胞相关。Aβ42 特异性淋巴细胞中 PDL-1 介导的凋亡的更高易感性和存在神经元的 BDNF 相关存活可能有助于 aMCI 中相对 CC 结构的保留。在 frank AD 中，这些潜在的保护机制丧失了，因为外周血中促炎细胞因子产生的 T 细胞反映了 CC 的严重改变。外周血中免疫细胞的监测在 AD 中可能具有预后价值。
