Roch J M, Masliah E, Roch-Levecq A C, Sundsmo M P, Otero D A, Veinbergs I, Saitoh T
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624.
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7450-4. doi: 10.1073/pnas.91.16.7450.
The secreted form (sAPP) of the Alzheimer amyloid beta/A4 protein precursor (APP) has been shown to be involved in the in vitro regulation of fibroblast growth and neurite extension from neuronal cells. The active site of sAPP responsible for these functions is within a small domain just C-terminal to the Kunitz-type protease inhibitor (KPI) insertion site. We report here that a 17-mer peptide, containing this active domain of sAPP, can induce cellular and behavioral changes when infused into rat brains. After 2 weeks of APP 17-mer peptide infusion, the animals were tested for reversal learning and memory retention and were sacrificed for morphological examination of brains. We found that administration of the APP 17-mer peptide resulted in an 18% increase in the number of presynaptic terminals in the frontoparietal cortex. At the behavioral level, 17-mer-infused animals with nonimpaired learning capability showed an increased memory retention that seemed to interfere with reversal learning performance. This APP 17-mer effect on memory retention was not observed in animals with impaired initial learning capacity. These results suggest that APP is involved in memory retention through its effect on synaptic structure.
阿尔茨海默病淀粉样β/A4蛋白前体（APP）的分泌形式（sAPP）已被证明参与体外成纤维细胞生长调节以及神经元细胞的神经突延伸。sAPP负责这些功能的活性位点位于紧挨着库尼茨型蛋白酶抑制剂（KPI）插入位点的C末端的一个小结构域内。我们在此报告，一种包含sAPP这个活性结构域的17肽，注入大鼠脑内时可诱导细胞和行为变化。在注入APP 17肽2周后，对动物进行反转学习和记忆保持测试，并将其处死后对大脑进行形态学检查。我们发现，给予APP 17肽导致额顶叶皮质中突触前终末数量增加了18%。在行为水平上，注入17肽且学习能力未受损的动物表现出记忆保持增强，这似乎干扰了反转学习表现。在初始学习能力受损的动物中未观察到这种APP 17肽对记忆保持的影响。这些结果表明，APP通过对突触结构的作用参与记忆保持。
