Quantitative in vivo measurement of early axonal transport deficits in a triple transgenic mouse model of Alzheimer's disease using manganese-enhanced MRI.
Quantitative in vivo measurement of early axonal transport deficits in a triple transgenic mouse model of Alzheimer's disease using manganese-enhanced MRI.
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DOI：
10.1016/j.neuroimage.2011.02.039
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发表时间：
2011-06-01
期刊：
影响因子：
5.7
通讯作者：
Lee P
中科院分区：
文献类型：
--
作者：
Kim J;Choi IY;Michaelis ML;Lee P
轴突运输受损与阿尔茨海默病（AD）的致病过程有关，其中轴突肿胀和变性是普遍存在的。发展非侵入性神经成像方法来定量评估体内轴突运输缺陷，对于早期观察阿尔茨海默病大脑的细微变化、监测疾病进展和量化药物干预的效果具有巨大的价值。一个三重转基因AD小鼠模型与人类AD神经病理学非常相似。在这项研究中，我们利用锰增强MRI快速多片T1定位，研究了三重转基因小鼠嗅觉系统纵向评估中轴突运输速率的年龄依赖性变化。数据显示，在这些小鼠的AD病理中，轴突运输损伤是一个非常早期的事件，在β斑块沉积和Tau原纤维形成之前。
Impaired axonal transport has been linked to the pathogenic processes of Alzheimer’s disease (AD) in which axonal swelling and degeneration are prevalent. The development of non-invasive neuroimaging methods to quantitatively assess in vivo axonal transport deficits would be enormously valuable to visualize early, yet subtle, changes in the AD brain, to monitor the disease progression and to quantify the effect of drug intervention. A triple transgenic mouse model of AD closely resembles human AD neuropathology. In this study, we investigated age-dependent alterations in the axonal transport rate in a longitudinal assessment of the triple transgenic mouse olfactory system, using fast multi-sliced T1 mapping with manganese-enhanced MRI. The data show that impairment in axonal transport is a very early event in AD pathology in these mice, preceding both deposition of Aβ plaques and formation of Tau fibrils.