Bartzokis George, Sultzer David, Lu Po H, Nuechterlein Keith H, Mintz Jim, Cummings Jeffrey L
Department of Neurology, Univeristy of California School of Medicine, Los Angeles, CA 90095, USA.
Neurobiol Aging. 2004 Aug;25(7):843-51. doi: 10.1016/j.neurobiolaging.2003.09.005.
Human and non-human primate data suggest that the structural integrity of myelin sheaths deteriorates during normal aging, especially in the late-myelinating association regions and may result in "disconnection" of widely distributed neural networks. Magnetic resonance imaging (MRI) was used to assess the heterogeneity of this process and its impact on brain aging and Alzheimer's disease (AD) by evaluating early- and later-myelinating regions of the corpus callosum, the splenium (Scc) and genu (Gcc), respectively. Calculated transverse relaxation rates (R2), an indirect measure of white matter structural integrity for the Gcc and Scc, were examined. The relationship between age and R2 differed in the two regions. A quadratic (inverted U) function with an accelerating rate of decline beginning at age 31 best represented the Gcc pattern while the Scc decline was three-fold smaller, gradual, and linear. These data suggest that the severity of age-related myelin breakdown is regionally heterogeneous, consistent with the hypothesis that differences in myelin properties make later-myelinating regions more susceptible to this process. In AD this process is globally exacerbated, consistent with an extracellular deleterious process such as amyloid beta-peptide toxicity. Non-invasive measures such as R2 may be useful in primary prevention studies of AD.
人类和非人类灵长类动物的数据表明，在正常衰老过程中，髓鞘的结构完整性会恶化，尤其是在髓鞘形成较晚的联合区域，这可能会导致广泛分布的神经网络“断开连接”。通过分别评估胼胝体的早期和晚期髓鞘形成区域、压部（Scc）和膝部（Gcc），利用磁共振成像（MRI）来评估这一过程的异质性及其对脑衰老和阿尔茨海默病（AD）的影响。研究了计算得到的横向弛豫率（R2），它是Gcc和Scc白质结构完整性的间接测量指标。两个区域的年龄与R2之间的关系有所不同。从31岁开始下降速度加快的二次（倒U形）函数最能代表Gcc的模式，而Scc的下降幅度小三倍，较为平缓且呈线性。这些数据表明，与年龄相关的髓鞘破坏的严重程度在区域上是异质的，这与髓鞘特性的差异使髓鞘形成较晚的区域更容易受到这一过程影响的假设一致。在AD中，这一过程在整体上会加剧，这与细胞外有害过程如淀粉样β肽毒性一致。像R2这样的非侵入性测量方法可能在AD的一级预防研究中有用。
