Ozturk M, de la Monte S M, Gross J, Wands J R
Molecular Hepatology Laboratory, Massachusetts General Hospital, Boston 02114.
Proc Natl Acad Sci U S A. 1989 Jan;86(2):419-23. doi: 10.1073/pnas.86.2.419.
We identified by a monoclonal antibody-based immunoradiometric assay high concentrations of an exocrine pancreatic protein called pancreatic thread protein (PTP) in several areas of Alzheimer disease (AD) brain. The saline-extractable soluble immunoreactivity shares at least three epitopes in common with the native pancreatic form of the protein; the Mr varies from approximately 17,000 to 20,000. Quantitative measurements of PTP immunoreactivity in various regions of several AD brains revealed levels varying from 12 to 295 ng/g of tissue (mean, 116 ng/g) compared with 1-11 ng/g of tissue (mean, 5 ng/g) found in comparable areas of control brains. Immunocytochemistry performed with the anti-PTP monoclonal antibodies demonstrate PTP immunoreactivity within large pyramidal neurons--many of which contain neurofibrillary tangles in both AD and Down syndrome. Less accumulation was observed in astrocytes, and some PTP immunoreactivity was found extracellularly. The highest number of labeled cells in AD and Down syndrome was seen in the hippocampal formation. Fewer positive-staining cells were noted in normal and disease control brains. We conclude, therefore, that an exocrine pancreatic protein is present in the central nervous system of normal individuals at low levels; in AD brain concentrations of this protein are much higher.
我们通过基于单克隆抗体的免疫放射分析发现在阿尔茨海默病（AD）脑的几个区域中存在高浓度的一种外分泌胰腺蛋白，称为胰腺丝蛋白（PTP）。盐水可提取的可溶性免疫反应性与该蛋白的天然胰腺形式至少有三个共同表位；其分子量约为17,000至20,000。对多个AD脑的不同区域中PTP免疫反应性的定量测量显示，其水平在12至295 ng/g组织之间变化（平均为116 ng/g），而在对照脑的相应区域中发现的水平为1至11 ng/g组织（平均为5 ng/g）。用抗PTP单克隆抗体进行的免疫细胞化学显示，在大锥体神经元内存在PTP免疫反应性，其中许多在AD和唐氏综合征中都含有神经原纤维缠结。在星形胶质细胞中观察到的积累较少，并且在细胞外发现了一些PTP免疫反应性。在AD和唐氏综合征中，标记细胞数量最多的是海马结构。在正常和疾病对照脑中观察到的阳性染色细胞较少。因此，我们得出结论，正常个体中枢神经系统中存在低水平的一种外分泌胰腺蛋白；在AD脑中，这种蛋白的浓度要高得多。
