Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy
Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy
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DOI：
10.1177/0271678x20944226
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发表时间：
2020-08-13
影响因子：
6.3
通讯作者：
Benveniste, Helene
中科院分区：
文献类型：
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作者：
Lee, Hedok;Xu, Feng;Benveniste, Helene
弥漫性白质病(WM)在老年脑小血管病(CSVD)中发病率较高。在人类中，脑淀粉样血管病(CAA)等cSVD通常与阿尔茨海默病并存，这对确定它们对WM的不同影响造成了重大障碍。在这里，我们在一种新的CAA 1型转基因大鼠模型(RTG-DI)中研究了与年龄相关的CAA病理对WM疾病的负担。使用MRI对RTG-DI和野生型大鼠进行纵向扫描，以表征形态测量、脑微出血(CMB)和WM完整性。在RTG-DI大鼠中，9个月和11个月时观察到明显的WM丢失模式，MRI还显示6个月时丘脑小CMB的表现，它先于WM丢失并逐渐扩大，直到病死期。组织学检查显示，所有RTG-DI大鼠的胼胝体和丘脑CMB均有髓鞘丢失，后者表现为靠近闭塞和钙化的微血管。RTG-DI大鼠CAA负荷的定量结果显示，微血管Aβ沉积最广泛的部位是丘脑。第一次使用活体磁共振成像，我们显示CAA 1型病理单独与WM丢失的独特模式相关。
Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular A beta deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.