Blennow K, Wallin A, Chong J K
Department of Clinical Neuroscience, University of Göteborg, Mölndal, Sweden.
Neurodegeneration. 1995 Jun;4(2):187-93. doi: 10.1006/neur.1995.0023.
Cerebrospinal fluid (CSF) biochemical markers for Alzheimer's disease (AD) would be of great value, both to improve clinical diagnostic accuracy and to increase our knowledge of the pathogenesis of the disorder. An increase in the CSF-level of 'neuronal thread protein' (pancreatic thread protein (PTP) immunoreactive material in the brain) has been suggested to be just such a biochemical marker. We have studied CSF 'neuronal thread protein'-like immunoreactivity (NTPLI) using a microparticle enzyme immunoassay. CSF-NTPLI did not differ significantly between AD type I (pure AD) and controls, but was significantly higher in AD type II (senile dementia) and vascular dementia (VAD) as compared with controls. Signs of blood-brain barrier (BBB) damage (elevated CSF/S albumin ratio) were found in both AD type II and in VAD, but not in AD type I. In a multiple ANOVA, with age and CSF/S albumin ratio as covariates, no significant difference in CSF-NTPLI between diagnostic groups was noted though both CSF/S albumin ratio and age (P < 0.0001 and P < 0.001 respectively) were found to influence the CSF-NTPLI level. Since BBB function was found to influence the CSF-NTPLI level, we examined whether NTPLI was present in serum. Indeed, serum NTPLI was about 40 times higher than CSF-NTPLI in neurological patients. Moreover, there was a statistically significant correlation between S-NTPLI and CSF-NTPLI. Taken together, present findings suggest that most of NTPLI in CSF comes from the serum, by passage over the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
用于阿尔茨海默病(AD)的脑脊液(CSF)生化标志物具有重要价值,既能提高临床诊断准确性,又能增进我们对该疾病发病机制的了解。有人提出脑脊液中“神经元纤维蛋白”(大脑中胰腺纤维蛋白(PTP)免疫反应性物质)水平升高就是这样一种生化标志物。我们使用微粒酶免疫测定法研究了脑脊液中“神经元纤维蛋白”样免疫反应性(NTPLI)。I型AD(单纯AD)患者与对照组的脑脊液NTPLI无显著差异,但II型AD(老年痴呆)和血管性痴呆(VAD)患者的脑脊液NTPLI显著高于对照组。在II型AD和VAD患者中均发现了血脑屏障(BBB)受损的迹象(脑脊液/血清白蛋白比值升高),但I型AD患者未出现。在一项多因素方差分析中,以年龄和脑脊液/血清白蛋白比值作为协变量,尽管发现脑脊液/血清白蛋白比值和年龄(分别为P < 0.0001和P < 0.001)均会影响脑脊液NTPLI水平,但各诊断组之间的脑脊液NTPLI无显著差异。由于发现血脑屏障功能会影响脑脊液NTPLI水平,我们检测了血清中是否存在NTPLI。事实上,神经系统疾病患者血清中的NTPLI比脑脊液中的NTPLI高约40倍。此外,血清NTPLI与脑脊液NTPLI之间存在统计学上的显著相关性。综上所述,目前的研究结果表明,脑脊液中的大多数NTPLI是通过血脑屏障从血清中来的。(摘要截短于250字)