Amlien I K, Fjell A M
Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.
Neuroscience. 2014 Sep 12;276:206-15. doi: 10.1016/j.neuroscience.2014.02.017. Epub 2014 Feb 27.
Alzheimer's disease (AD) has traditionally been regarded as a disease of the gray matter (GM). However, the advent of diffusion tensor imaging (DTI) has contributed to new knowledge about how changes in white matter (WM) microstructure in vivo may be directly related to the pathophysiology of AD. It is now evident that WM is heavily affected in AD, even at early stages. Still, our knowledge about WM degeneration in AD is poor compared to what we know about GM atrophy. For instance, it has not been clear if WM can be directly affected in AD independently of GM degeneration, or whether WM changes mainly represent secondary effects of GM atrophy, e.g. through Wallerian degeneration. In this paper, we review recent studies using DTI to study WM alterations in AD. These studies suggest that microstructural WM affection at pre-AD stages cannot completely be accounted for by concomitant GM atrophy. Further, recent research has demonstrated relationships between increased cerebrospinal fluid levels of Tau proteins and changes in WM microstructure indexed by DTI, which could indicate that WM degeneration in pre-AD stages is related to ongoing axonal damage. We conclude that DTI is a promising biomarker for AD, with the potential also to identify subgroups of patients with especially high degree of WM affection, thereby contributing to more differentiated pre-AD diagnoses. However, more research and validation studies are needed before it is realistic to use this information in clinical practice with individual patients.
传统上，阿尔茨海默病（AD）被视为一种灰质（GM）疾病。然而，扩散张量成像（DTI）的出现为我们带来了新的认识，即活体白质（WM）微观结构的变化如何可能与AD的病理生理学直接相关。现在很明显，即使在早期阶段，AD患者的WM也受到严重影响。尽管如此，与我们对GM萎缩的了解相比，我们对AD中WM变性的认识仍然不足。例如，目前尚不清楚AD中WM是否能独立于GM变性而直接受到影响，或者WM变化是否主要代表GM萎缩的继发效应，例如通过华勒氏变性。在本文中，我们回顾了最近使用DTI研究AD中WM改变的研究。这些研究表明，AD前期阶段WM微观结构的改变不能完全用伴随的GM萎缩来解释。此外，最近的研究表明，脑脊液中Tau蛋白水平升高与DTI所显示的WM微观结构变化之间存在关联，这可能表明AD前期阶段的WM变性与正在进行的轴突损伤有关。我们得出结论，DTI是一种有前景的AD生物标志物，也有可能识别出WM受影响程度特别高的患者亚组，从而有助于更具针对性的AD前期诊断。然而，在将这些信息应用于个体患者的临床实践之前，还需要更多的研究和验证性研究。
