Delatour Benoît, Guégan Maryvonne, Volk Andreas, Dhenain Marc
Laboratoire NAMC, CNRS, UMR 8620, Bât 446, Université Paris Sud, 91405 Orsay, France.
Neurobiol Aging. 2006 Jun;27(6):835-47. doi: 10.1016/j.neurobiolaging.2005.04.011. Epub 2005 Jul 14.
Regional cerebral atrophy was evaluated in APP/PS1 mice harboring mutated transgenes linked to familial Alzheimer's disease, using complementary methods. In vivo high resolution MRI was selected for measurements of brain atrophy and associated cerebrospinal fluid dilation; histological analysis was performed to reveal localized atrophies and to evaluate amyloid burden. Young APP/PS1 mice examined at a pre-amyloid stage (10 weeks) showed disruption in development (reduced intracranial and brain volumes). Comparison of young and old (24 months) mice, indicated that both APP/PS1 and control brains endure growth during adulthood. Aged APP/PS1 animals showed a moderate although significant global brain atrophy and a dilation of CSF space in posterior brain regions. The locus of this atrophy was identified in the midbrain area and not, as expected, at isocortical/hippocampal levels. Atrophy was also detected in fiber tracts. The severity of brain atrophy in old APP/PS1 mice was not correlated with the extent of cerebral amyloidosis. The relevance of current transgenic mouse models for the study of brain atrophy related to Alzheimer's disease is discussed.
采用互补方法，对携带与家族性阿尔茨海默病相关的突变转基因的APP/PS1小鼠的局部脑萎缩进行了评估。选择体内高分辨率MRI来测量脑萎缩和相关的脑脊液扩张；进行组织学分析以揭示局部萎缩并评估淀粉样蛋白负荷。在淀粉样蛋白前阶段（10周）检查的年轻APP/PS1小鼠表现出发育中断（颅内和脑体积减小）。年轻和年老（24个月）小鼠的比较表明，APP/PS1小鼠和对照小鼠的大脑在成年期都会生长。老年APP/PS1动物表现出中度但显著的全脑萎缩以及后脑区域脑脊液空间扩张。这种萎缩的部位在中脑区域被确定，而不是如预期的在等皮质/海马水平。在纤维束中也检测到了萎缩。老年APP/PS1小鼠脑萎缩的严重程度与脑淀粉样变性的程度无关。讨论了当前转基因小鼠模型在研究与阿尔茨海默病相关的脑萎缩方面的相关性。
