中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 775-779.doi: 10.4103/1673-5374.295340

• 原著:退行性病与再生 • 上一篇    下一篇

阿尔茨海默病早期诊断标志物:外周血受激活调节正常T细胞表达和分泌因子

  

  • 出版日期:2021-04-15 发布日期:2020-12-22

Regulated upon activation, normal T cell expressed and secreted (RANTES) levels in the peripheral blood of patients with Alzheimer’s disease

Gabriela Vacínová1, 2, *, Daniela Vejražkova1, Robert Rusina3, Iva Holmerová4, 5, Hana Vaňková4, Eva Jarolímová4, Josef Včelák1, Běla Bendlová1, Markéta Vaňková1#br#   

  1. 1 Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic;  2 Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic;  3 Department of Neurology, Third Faculty of Medicine of Charles University and Thomayer Hospital Prague, Czech Republic;  4 II. Internal Medicine Clinic, Third Faculty of Medicine, Charles University, Prague, Czech Republic;  5 Faculty of Humanitites, Charles University Prague, Czech Republic
  • Online:2021-04-15 Published:2020-12-22
  • Contact: Gabriela Vacínová, PhD, vacinovagabriela@gmail.com.
  • Supported by:
    This work was supported by the grant MH CZ NV 18-01-00399 from the Czech Ministry of Health.

摘要:

许多研究者试图寻找阿尔茨海默病发病早期诊断标志物,以延缓阿尔茨海默病进展。受激活调节正常T细胞表达和分泌因子(RANTES)是一种参与T细胞和其他淋巴样细胞迁移的趋化因子,其在神经退行性疾病(如帕金森病和多发性硬化症)血液或脑脊液中的表达有变化。为了解阿尔茨海默病患者外周血中的RANTES水平变化,这项观察性研究纳入85例早期阿尔茨海默病患者(男39例,女46例;平均年龄75.7岁)和78名正常对照受试者(男24名,女54名;平均年龄66岁),对其血浆RANTES水平进行检测。结果发现:(1)与对照组相比,阿尔茨海默病患者血浆RANTES的水平更高;(2)阿尔茨海默病患者RANTES水平与年龄、疾病持续时间、Fazekas量表评分和颞叶内侧萎缩(MTA)评分呈负相关,即最高水平对应疾病的早期阶段;(3)在阿尔茨海默病患者中,RANTES与促炎细胞因子白细胞介素6,肿瘤坏死因子α,胰岛素水平,胰岛素抵抗(HOMA-R)和胰腺β细胞功能(HOMA-F)呈正相关;(4)这项研究评估了可能影响RANTES血浆水平的几种临床和代谢因素,但不能解释阿尔茨海默病患者中RANTES水平的升高,可将血浆RANTES的水平视为阿尔茨海默病早期阶段标志物。

https://orcid.org/0000-0002-9283-519X (Gabriela Vacínová)

Abstract: Alzheimer’s disease (AD) is the most common type of dementia, but it is very difficult to diagnose with certainty, so many AD studies have attempted to find early and relevant diagnostic markers. Regulated upon activation, normal T cell expressed and secreted (RANTES, also known as C-C chemokine ligand) is a chemokine involved in the migration of T cells and other lymphoid cells. Changes in RANTES levels and its expression in blood or in cerebrospinal fluid have been reported in some neurodegenerative diseases, such as Parkinson’s disease and multiple sclerosis, but also in metabolic diseases in which inflammation plays a role. The aim of this observational study was to assess RANTES levels in peripheral blood as clinical indicators of AD. Plasma levels of RANTES were investigated in 85 AD patients in a relatively early phase of AD (median 8.5 months after diagnosis; 39 men and 46 women; average age 75.7 years), and in 78 control subjects (24 men and 54 women; average age 66 years). We found much higher plasma levels of RANTES in AD patients compared to controls. A negative correlation of RANTES levels with age, disease duration, Fazekas scale score, and the medial temporal lobe atrophy (MTA) score (Scheltens’s scale) was found in AD patients, i.e., the higher levels corresponded to earlier stages of the disease. Plasma RANTES levels were not correlated with cognitive scores. In AD patients, RANTES levels were positively correlated with the levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, which is consistent with the well-known fact that AD is associated with inflammatory processes. RANTES levels were also positively correlated with insulin levels in AD patients, with insulin resistance (HOMA-R) and pancreatic beta cell function (HOMA-F). This study evaluated several clinical and metabolic factors that may affect plasma levels of RANTES, but these factors could not explain the increases in RANTES levels observed in AD patients. Plasma levels of RANTES appear to be an interesting peripheral marker for early stages of AD. The study was approved by the Ethics Committee of Institute of Endocrinology, Prague, Czech Republic on July 22, 2011.

Key words: Alzheimer’s disease, biomarker, central nervous system, cognitive impairment, inflammation, RANTES