Philipson Ola, Lannfelt Lars, Nilsson Lars N G
Department of Public Health and Caring Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
FEBS Lett. 2009 Sep 17;583(18):3021-6. doi: 10.1016/j.febslet.2009.08.009. Epub 2009 Aug 14.
Intraneuronal punctate immunostaining in Alzheimer's disease brain and amyloid-beta precursor protein (APP) transgenic mice has been suggested to represent Abeta, but this is somewhat controversial. Here we show that both biochemical Abeta levels and intraneuronal immunostaining are reduced in APP transgenic mice when gamma-secretase is inhibited. Moreover, BACE-1 deficient APP transgenic mice show neither Abeta production nor intraneuronal immunostaining. Our findings suggest that the punctate immunostaining with APP antibodies is due to Abeta that has accumulated inside neurons. Similar type of intraneuronal Abeta accumulation, which precedes senile plaque formation, may link Abeta to tauopathy and neurodegeneration in Alzheimer's disease pathogenesis.
阿尔茨海默病大脑和淀粉样前体蛋白（APP）转基因小鼠中的神经元内点状免疫染色被认为代表β淀粉样蛋白（Aβ），但这在一定程度上存在争议。在此我们表明，当γ-分泌酶被抑制时，APP转基因小鼠中的生化Aβ水平和神经元内免疫染色均降低。此外，BACE-1缺陷的APP转基因小鼠既不产生Aβ，也没有神经元内免疫染色。我们的研究结果表明，用APP抗体进行的点状免疫染色是由于在神经元内积累的Aβ所致。在老年斑形成之前出现的类似类型的神经元内Aβ积累，可能在阿尔茨海默病发病机制中将Aβ与tau病变和神经退行性变联系起来。
