The mechanism of cerebral accumulation of amyloid protein and aluminum.

阿尔茨海默病的特点是淀粉样蛋白在大脑细胞外沉积。淀粉样蛋白在脑内积累的机制尚不清楚，也没有报道过产生细胞外淀粉样蛋白的简单模型系统。这里我们推测淀粉样蛋白是由脑溶酶体中淀粉样前体蛋白的降解产生的。为了研究淀粉样蛋白在脑内产生的细胞机制，需要纯度高且特征明确的脑溶酶体片段。因此，我们试图从大鼠脑中获得纯度更高、产量高的溶酶体部分，使用Percoll梯度，在钙存在的情况下使线粒体肿胀，从而消除少量线粒体的污染。脑溶酶体被纯化了330倍，收率约为22%，是所有脑溶酶体制剂中最高的。Burkart等人（1982）报道，脑溶酶体可能不仅在降解大分子方面发挥重要作用，而且在将大分子运送到沉积部位方面也发挥重要作用。因此，获得纯化的大鼠脑溶酶体应该是研究在脑中积累的大分子的产生及其分泌和/或运输的重要一步。

Alzheimer's disease is characterized by extracellular deposition in the brain of amyloid protein. The mechanism of accumulation of amyloid in brain is unknown and no simple model systems that produce extracellular amyloid have been reported. Here we speculate that the amyloid protein is generated from the degradation of amyloid precursor protein in cerebral lysosomes. To study the cellular mechanism of generation of the amyloid protein in the brain, pure and well characterized cerebral lysosomal fraction is needed. Therefore, we attempted to obtain a lysosomal fraction from rat brain which had a higher degree of purity in good yield using Percoll gradients following the swelling of mitochondria in the presence of calcium which would eliminate contamination from small amounts of mitochondria. Cerebral lysosomes were purified 330-fold with a yield of approximately 22%, which the highest reported for any cerebral lysosomal preparation. Burkart et al. (1982) have reported that brain lysosomes may play a major role not only in degrading macromolecules but also in their transport to the deposition site. Therefore, obtaining purified rat cerebral lysosomes should represent an important step in the study of the generation of macromolecules which accumulate in the brain and their secretion and/or transport.