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阿尔茨海默病中中枢神经系统炎症与退变标志物和血脑屏障损伤之间的关系

The Relationship between Markers of Inflammation and Degeneration in the Central Nervous System and the Blood-Brain Barrier Impairment in Alzheimer's Disease.

作者信息

Muszyński Paweł, Kulczyńska-Przybik Agnieszka, Borawska Renata, Litman-Zawadzka Ala, Słowik Agnieszka, Klimkowicz-Mrowiec Aleksandra, Pera Joanna, Dziedzic Tomasz, Mroczko Barbara

机构信息

Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Poland.

Department of Neurology, Jagiellonian University, Kraków, Poland.

出版信息

J Alzheimers Dis. 2017;59(3):903-912. doi: 10.3233/JAD-170220.

DOI:10.3233/JAD-170220
PMID:28697565
Abstract

BACKGROUND

It is known that YKL-40- a marker of glial inflammation, and VILIP-1- a marker of neuronal injury, reflect functional and structural changes in AD brains, although there is limited data concerning their potential influence on blood-brain barrier (BBB) homeostasis.

OBJECTIVE

Therefore, the aim of our study was to investigate the relationship between markers of inflammation and degeneration in the central nervous system (CNS) of patients with AD and mild cognitive impairment (MCI) as well as immunological response in CNS and BBB function.

METHODS

Cerebrospinal fluid (CSF) concentrations of proteins tested were determined in 45 AD patients, 18 MCI subjects, and 23 non-demented controls using ELISA method.

RESULTS

CSF concentrations of YKL-40 were significantly higher in MCI and AD patients, whereas CSF levels of VILIP-1 were statistically higher in the AD group as compared to the subjects without cognitive deficits. Elevated concentrations of YKL-40 correlated significantly with increased albumin quotient and decreased Aβ42/40 ratio in AD patients and with IgG quotient in the total study group. We did not find a relationship between VILIP-1 and immunological parameters reflecting BBB dysfunction and humoral immune response.

CONCLUSION

Our findings indicate that YKL-40 may contribute to decreased stability and increased permeability of BBB in AD patients. It is assumed that YKL-40 is implicated in the development of brain barriers, although its precise mechanism of action in the BBB disruption remains unrevealed. Further studies on larger groups of patients are required to confirm our hypothesis.

摘要

背景

已知YKL - 40(一种神经胶质炎症标志物)和VILIP - 1(一种神经元损伤标志物)反映了阿尔茨海默病(AD)大脑中的功能和结构变化,尽管关于它们对血脑屏障(BBB)稳态潜在影响的数据有限。

目的

因此,我们研究的目的是调查AD和轻度认知障碍(MCI)患者中枢神经系统(CNS)中炎症和变性标志物之间的关系,以及CNS中的免疫反应和BBB功能。

方法

使用酶联免疫吸附测定(ELISA)方法测定了45例AD患者、18例MCI受试者和23例非痴呆对照者脑脊液(CSF)中检测的蛋白质浓度。

结果

MCI和AD患者的CSF中YKL - 40浓度显著更高,而与无认知缺陷的受试者相比,AD组的CSF中VILIP - 1水平在统计学上更高。AD患者中YKL - 40浓度升高与白蛋白商增加、Aβ42/40比值降低显著相关,在整个研究组中与IgG商相关。我们未发现VILIP - 1与反映BBB功能障碍和体液免疫反应的免疫参数之间存在关联。

结论

我们的研究结果表明,YKL - 40可能导致AD患者BBB稳定性降低和通透性增加。据推测,YKL - 40与脑屏障的发展有关,尽管其在BBB破坏中的精确作用机制仍未揭示。需要对更大规模的患者群体进行进一步研究以证实我们的假设。

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