Slunt H H, Thinakaran G, Von Koch C, Lo A C, Tanzi R E, Sisodia S S
Neuropathology Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.
J Biol Chem. 1994 Jan 28;269(4):2637-44.
Alzheimer's disease is characterized by the presence of senile plaques comprised primarily of deposits of the beta-amyloid protein (A beta) derived from larger amyloid precursor proteins (APP). We have identified a cDNA that encodes a 751-amino acid APP-like protein (designated APLP2) from the mouse that, with exception of the A beta region, is highly homologous to APP. In situ hybridization and quantitative polymerase chain reaction reveal that APLP2 and APP mRNA are expressed in similar, if not identical, neuronal populations and at similar levels. APLP2 appears to mature through the same unusual secretory/cleavage pathway as APP. Furthermore, widely utilized antibodies generated against non-overlapping epitopes of APP do not discriminate between APP and APLP2. Although APLP2 cannot give rise to A beta, its near identity to APP outside the A beta domain confounds the interpretation of previous immunocytochemical and biochemical characterizations of APP biosynthesis and metabolism.
阿尔茨海默病的特征是存在主要由源自较大淀粉样前体蛋白（APP）的β-淀粉样蛋白（Aβ）沉积物组成的老年斑。我们从小鼠中鉴定出一种编码751个氨基酸的APP样蛋白（命名为APLP2）的cDNA，该蛋白除Aβ区域外，与APP高度同源。原位杂交和定量聚合酶链反应显示，APLP2和APP mRNA在相似（如果不是相同）的神经元群体中以相似水平表达。APLP2似乎通过与APP相同的异常分泌/切割途径成熟。此外，针对APP不重叠表位产生的广泛使用的抗体无法区分APP和APLP2。尽管APLP2不能产生Aβ，但其在Aβ结构域外与APP的高度相似性混淆了先前对APP生物合成和代谢的免疫细胞化学和生化特征的解释。
