Detection of vascular alterations by in vivo magnetic resonance angiography and histology in APP/PS1 mouse model of Alzheimer's disease
Detection of vascular alterations by in vivo magnetic resonance angiography and histology in APP/PS1 mouse model of Alzheimer's disease
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DOI：
10.1007/s10334-009-0194-y
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发表时间：
2010-02-01
影响因子：
2.3
通讯作者：
Dhenain, Marc
中科院分区：
文献类型：
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作者：
El Tayara, Nadine El Tannir;Delatour, Benoit;Dhenain, Marc
阿尔茨海默病（AD）患者的大脑以淀粉样斑块和神经原纤维缠结的存在为特征。血管改变，如淀粉样血管病也常在AD患者中报道，并参与疾病发生和进展的机制。转基因阿尔茨海默病小鼠模型已被设计用于评估该疾病的病理生理和新的治疗方法。我们的研究评估了APP(SweLon)/PS1(M146L) AD小鼠模型的血管改变。采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。组织学分析表明，脑血管淀粉样蛋白沉积与细胞外淀粉样斑块同时开始。然而，与斑块沉积不同，脑血管病变的严重程度在老年动物中是稳定的。老年APP(SweLon)/PS1（M146L）小鼠相对于成年小鼠，通过TOF和ce血管造影评估血管空洞的严重程度和血管长度的减少，检测到大脑中动脉的改变。对照PS1小鼠的年龄相关改变仅在ce血管造影上检测到血管长度减少。这些结果表明，宏观血管异常是APP(SweLon)/PS1(M146L) AD小鼠模型病理改变的一部分。
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.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.