Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer T A
Department of Psychiatry, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany.
Neurosci Lett. 2001 Jun 22;306(1-2):116-20. doi: 10.1016/s0304-3940(01)01876-6.
beta-Amyloid peptides are key molecules that are involved in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Abeta, however, is still a matter of controversial debates. In the present report, we studied the neuropathological events in a transgenic mouse model expressing human mutant beta-amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular Abeta staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic Abeta positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal Abeta staining was no longer detected in the brain of aged double-transgenic mice, which correlates with the typical neuropathology in the brain of chronic AD patients.
β-淀粉样肽是参与阿尔茨海默病(AD)病理过程的关键分子。然而,β-淀粉样蛋白(Aβ)神经毒性作用的来源和部位仍是一个有争议的话题。在本报告中,我们研究了在神经元中表达人类突变型β-淀粉样前体蛋白和人类突变型早老素-1的转基因小鼠模型中的神经病理事件。蛋白质免疫印迹和免疫组织化学分析显示,细胞内Aβ染色先于斑块沉积,斑块沉积始于海马结构。在后期,在所有皮质、海马和许多其他脑区发现了许多神经炎性Aβ阳性斑块。有趣的是,在老年双转基因小鼠的大脑中未再检测到神经元内Aβ染色,这与慢性AD患者大脑中的典型神经病理学相关。