Aβ deposition and related pathology in an APP x PS1 transgenic mouse model of Alzheimer's disease
Aβ deposition and related pathology in an APP x PS1 transgenic mouse model of Alzheimer's disease
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DOI：
10.14670/hh-23.67
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发表时间：
2008-01-01
影响因子：
2
通讯作者：
Richardson, J. C.
中科院分区：
文献类型：
--
作者：
Howlett, D. R.;Bowler, K.;Richardson, J. C.
携带与阿尔茨海默病（AD）家族性形式相关的淀粉样前体蛋白和早老素-1（TASTPM）突变转基因的转基因小鼠在相关的脑病理学中显示AB斑块沉积和年龄相关的组织学变化。存在的AB具有多种形式，包括在位置40或42处具有C-末端以及在位置1处具有N-末端或以焦-3-谷氨酸形式截短的种类。沉积物中还存在内源性啮齿动物AB。激光捕获显微切割提取物显示AB的多聚体形式存在于斑块和斑块周围组织中。与AB沉积物相关的是以星形胶质细胞的存在为特征的炎症反应的证据。与沉积物密切相关的还有磷酸化tau蛋白和组织蛋白酶D免疫标记。星形胶质细胞和磷酸化tau蛋白和组织蛋白酶D负荷的发生率表明，这两种潜在的疾病标志物与小鼠的年龄和AB沉积平行增加。TASTPM小鼠皮层和海马神经元的免疫组织化学标记表明，AB沉积的区域与神经元的损失有关。因此，TASTPM小鼠表现出AD疾病进展的许多病理学特征，并可提供用于评估针对改变或停止疾病进展的新型治疗剂的手段。
A transgenic mouse bearing mutant transgenes linked to familial forms of Alzheimer's disease ( AD) for the amyloid precursor protein and presenilin-1 (TASTPM) showed AB plaque deposition and age-related histological changes in associated brain pathology. The AB present was of multiple forms, including species with a C-terminus at position 40 or 42, as well as an N-terminus at position 1 or truncated in a pyro-3-glutamate form. Endogenous rodent AB was also present in the deposits. Laser capture microdissection extracts showed that multimeric forms of AB were present in both plaque and tissue surrounding plaques. Associated with the AB deposits was evidence of an inflammatory response characterised by the presence of astrocytes. Also present in close association with the deposits was phosphorylated tau and cathepsin D immunolabelling. The incidence of astrocytes and of phosphorylated tau and cathepsin D load showed that both of these potential disease markers increased in parallel to the age of the mice and with AB deposition. Immunohistochemical labelling of neurons in the cortex and hippocampus of TASTPM mice suggested that the areas of AB deposition were associated with the loss of neurons. TASTPM mice, therefore, exhibit a number of the pathological characteristics of disease progression in AD and may provide a means for assessment of novel therapeutic agents directed towards modifying or halting disease progression.