de la Monte S M, Ozturk M, Wands J R
Molecular Hepatology Laboratory, Massachusetts Alzheimer's Disease Research Center, Charlestown 02114.
J Clin Invest. 1990 Sep;86(3):1004-13. doi: 10.1172/JCI114762.
Pancreatic thread protein (PTP) is a major exocrine secretory protein that in vitro forms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD). We previously described increased PTP immunoreactivity in AD brains and now report high levels in the developing human brain. Using a full-length cloned bovine PTP cDNA and synthetic oligonucleotides corresponding to human PTP cDNA, which is identical to human islet cell regeneration factor, we analyzed the expression of PTP in pancreas and brain. A major 0.9-kb as well as several minor transcripts were identified in human pancreas. In AD brain, the same size transcripts were detected by Northern analysis, primer extension assay, or polymerase chain reaction amplification of cDNAs generated by reverse transcriptase assay. There were significantly higher levels of PTP mRNA in brains with AD compared with aged controls, with increased amounts of 1.2-, 0.6-, and 0.4-kb transcripts by Northern analysis. In situ hybridization localized expression to pyramidal neurons in the cerebral cortex, the same population that contains neurofibrillary tangles and high levels of immunoreactive PTP. These findings suggest that AD is associated with enhanced expression of PTP-related transcripts with intraneuronal accumulation of PTP-like proteins.
胰腺丝蛋白（PTP）是一种主要的外分泌分泌蛋白，在体外形成的丝状束让人联想到阿尔茨海默病（AD）的双螺旋丝。我们之前描述过AD脑内PTP免疫反应性增加，现在报告其在发育中的人类大脑中水平也很高。利用全长克隆的牛PTP cDNA以及与人PTP cDNA对应的合成寡核苷酸（后者与人胰岛细胞再生因子相同），我们分析了PTP在胰腺和大脑中的表达。在人胰腺中鉴定出一个主要的0.9 kb转录本以及几个次要转录本。在AD脑中，通过Northern分析、引物延伸试验或逆转录酶试验生成的cDNA的聚合酶链反应扩增检测到相同大小的转录本。与老年对照组相比，AD脑中PTP mRNA水平显著更高，通过Northern分析发现1.2 kb、0.6 kb和0.4 kb转录本的量增加。原位杂交将表达定位到大脑皮质的锥体细胞，这一细胞群体含有神经原纤维缠结和高水平的免疫反应性PTP。这些发现表明，AD与PTP相关转录本的表达增强以及PTP样蛋白在神经元内的积累有关。
