Institut Curie, Centre de Recherche, Orsay, France.
MAGMA. 2010 Feb;23(1):53-64. doi: 10.1007/s10334-009-0194-y.
The brain of patients with Alzheimer's disease (AD) is characterized by the presence of amyloid plaques and neurofibrillary tangles. Vascular alterations such as amyloid angiopathy are also commonly reported in patients with AD and participate in mechanisms involved in disease onset and progression. Transgenic mouse models of AD have been engineered to evaluate the pathophysiology and new treatments of the disease. Our study evaluated vascular alterations in APP(SweLon)/PS1(M146L) mouse model of AD.
Histological analysis and in vivo magnetic resonance angiography protocols based on time of flight (TOF) and contrast-enhanced (CE) angiography were applied to evaluate cerebrovascular alterations. Results Histological analysis showed that cerebrovascular amyloid deposition starts by the same time as extracellular amyloid plaques. However, unlike plaques deposition, severity of cerebrovascular alterations is stabilized in older animals. Alteration of the middle cerebral artery was detected in old APP(SweLon)/PS1(M146L) mice with respect to adult ones by evaluating the severity of vessel voids and the reduction of vessel length on TOF- and CE-angiograms. Age-related alterations in control PS1 mice were only detected as a reduced vessel length on CE-angiograms.
These results show that macroscopic vascular abnormalities are part of the pathological alterations developed by APP(SweLon)/PS1(M146L) mouse models of AD.
阿尔茨海默病（AD）患者的大脑以存在淀粉样斑块和神经纤维缠结为特征。血管改变，如淀粉样血管病，在 AD 患者中也很常见，并参与疾病发病和进展的机制。AD 的转基因小鼠模型已被设计用于评估疾病的病理生理学和新的治疗方法。我们的研究评估了 APP(SweLon)/PS1(M146L)AD 转基因小鼠模型中的血管改变。
应用组织学分析和基于飞行时间 (TOF) 和对比增强 (CE) 血管造影的体内磁共振血管造影方案来评估脑血管改变。结果组织学分析显示，脑血管淀粉样沉积与细胞外淀粉样斑块同时开始。然而，与斑块沉积不同，脑血管改变的严重程度在老年动物中稳定。通过评估 TOF 和 CE 血管造影上血管空洞的严重程度和血管长度的减少，发现老年 APP(SweLon)/PS1(M146L)小鼠的大脑中动脉发生了改变，而成年 APP(SweLon)/PS1(M146L)小鼠则没有。在 PS1 对照小鼠中，仅在 CE 血管造影上检测到与年龄相关的血管长度减少。
这些结果表明，宏观血管异常是 APP(SweLon)/PS1(M146L)AD 转基因小鼠模型中发展的病理改变的一部分。
