APPswe转基因小鼠会出现与年龄相关的β淀粉样蛋白沉积和神经纤维异常，但CA1区无神经元丢失。

APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.

作者信息

Irizarry M C, McNamara M, Fedorchak K, Hsiao K, Hyman B T

机构信息

Department of Neurology, Massachusetts General Hospital, Boston, USA.

出版信息

J Neuropathol Exp Neurol. 1997 Sep;56(9):965-73. doi: 10.1097/00005072-199709000-00002.

DOI:10.1097/00005072-199709000-00002

PMID:9291938

Abstract

The recent availability of transgenic mouse models of Alzheimer disease has allowed direct in vivo assessment of the molecular and neuropathological effects of cerebral amyloid deposition. We examined 16-month-old Tg(HuAPP695. K670N-M671L)2576 mice expressing human APP K670N-M671L (APPSw), which have amyloid deposition and behavioral deficits by 11 months of age. Transgene expression is predominantly neuronal, and results in amyloid deposits, comparable to human senile plaques, at terminal zones of transgene positive neurons in cortical and limbic regions. Amyloid deposits were associated with prominent gliosis and neuritic dystrophy, without neuronal loss in CA1, loss of synaptophysin immunoreactivity in the hippocampal dentate gyrus, or loss of messenger RNA for neuronal synaptic, cytoskeletal, or metabolic proteins. We conclude that A beta is not acutely neurotoxic, but can disrupt neuronal processes and provoke an inflammatory response.

摘要

最近阿尔茨海默病转基因小鼠模型的出现，使得对脑淀粉样蛋白沉积的分子和神经病理学效应进行直接的体内评估成为可能。我们研究了16月龄的Tg(HuAPP695.K670N-M671L)2576小鼠，这些小鼠表达人APP K670N-M671L（APPSw），在11月龄时就有淀粉样蛋白沉积和行为缺陷。转基因表达主要在神经元中，导致在皮质和边缘区域转基因阳性神经元的终末区出现与人类老年斑相当的淀粉样蛋白沉积。淀粉样蛋白沉积与显著的胶质细胞增生和神经突营养不良相关，没有CA1区的神经元丢失、海马齿状回中突触素免疫反应性的丧失，或神经元突触、细胞骨架或代谢蛋白信使RNA的丢失。我们得出结论，β淀粉样蛋白不是急性神经毒性的，但会破坏神经元过程并引发炎症反应。