CHROMOGRANIN-A IN CEREBROSPINAL-FLUID - A BIOCHEMICAL MARKER FOR SYNAPTIC DEGENERATION IN ALZHEIMERS-DISEASE
CHROMOGRANIN-A IN CEREBROSPINAL-FLUID - A BIOCHEMICAL MARKER FOR SYNAPTIC DEGENERATION IN ALZHEIMERS-DISEASE
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DOI：
10.1159/000106963
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发表时间：
1995-11-01
期刊：
影响因子：
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通讯作者：
EKMAN, R
中科院分区：
文献类型：
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作者：
BLENNOW, K;DAVIDSSON, P;EKMAN, R
对阿尔茨海默病的生化标志物的研究对于提高临床诊断的准确性和增加对该病发病机制的认识具有重要的价值。阿尔茨海默病的主要特征之一是突触退化。因此，我们研究了脑脊液（CSF）中染色质蛋白A （CrA）是否可能作为阿尔茨海默病突触功能的生化标志物。脑脊液中CrA的平均浓度约为血清中CrA浓度的7.5倍，CSF-CrA与血脑屏障功能（以CSF/血清白蛋白比测量）之间无显著相关性，CSF-CrA与血清CrA之间也无显著相关性。这些发现表明，CSF-CrA的主要部分是在中枢神经系统内局部产生的。AD组（n = 29）、血管性痴呆组（n = 13）和年龄匹配对照组（n = 9）之间的CSF-CrA水平无显著差异（分别为99.9 +/- 58.9 ng/ml、108.0 +/- 69.4 ng/ml和115.1 +/- 44.4 ng/ml）。然而，当将AD组细分为AD I型（n = 12）和AD II型（n = 17）时，AD I型患者CSF-CrA浓度（72.8 +/- 28.9 ng/ml）低于对照组（115.1 +/- 44.4 ng/ml）， p < 0.02， AD II型患者CSF-CrA浓度（119.1 +/- 67.5 ng/ml）， p < 0.05，而AD II型与对照组之间CSF-CrA无显著差异。这些发现提示CSF-CrA有可能作为AD I型突触变性的生化标志物，并进一步支持在科学研究中识别AD I型（纯AD）亚群的相关性。
Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid (CSF) may be of value as a biochemical marker for the synaptic function in AD. The mean concentration of CrA in CSF was about 7.5 times higher than its concentration in serum, and there was no significant correlation between CSF-CrA and the blood-brain barrier function (measured as the CSF/serum albumin ratio), nor between CSF-CrA and serum-CrA. These findings suggest that the major portion of CSF-CrA is locally produced within the CNS. There were no significant differences in CSF-CrA between the AD (n = 29), vascular dementia (n = 13), and age-matched control (n = 9) groups (99.9 +/- 58.9 ng/ml, 108.0 +/- 69.4 ng/ml, and 115.1 +/- 44.4 ng/ml, respectively). However, when the AD group was subdivided into AD type I (n = 12) and AD type II (n = 17), a lower concentration of CSF-CrA was found in AD type I (72.8 +/- 28.9 ng/ml) compared with controls (115.1 +/- 44.4 ng/ml), p < 0.02, and compared with AD type II (119.1 +/- 67.5 ng/ml), p < 0.05, while CSF-CrA did not significantly differ between AD type II and controls. These findings suggest that CSF-CrA has a potential as a biochemical marker for the synaptic degeneration in AD type I, and gives further support for the relevance of identifying the AD type I (pure AD) subgroup in scientific studies.