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针对血管紧张素2 1型受体的自身抗体:阿尔茨海默病中的一种新型自身抗体。

Autoantibodies Toward the Angiotensin 2 Type 1 Receptor: A Novel Autoantibody in Alzheimer's Disease.

作者信息

Giil Lasse M, Kristoffersen Einar K, Vedeler Christian A, Aarsland Dag, Nordrehaug Jan Erik, Winblad Bengt, Cedazo-Minguez Angel, Lund Anders, Reksten Tove Ragna

机构信息

Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.

Institute of Clinical Science, University of Bergen, Bergen, Norway.

出版信息

J Alzheimers Dis. 2015;47(2):523-9. doi: 10.3233/JAD-150053.

Abstract

BACKGROUND

Autoantibodies with agonist function are described in cardiovascular disorders. Since vascular risk factors are associated with an increased risk for Alzheimer's disease (AD), we investigated a potential association between antibodies to the angiotensin 2 type 1 receptor (anti-AT1R) and AD.

OBJECTIVE

The primary objective of this study was to investigate the association between anti-AT1R and AD. The secondary objective was to investigate the association between clinical or biomarker features of AD and anti-AT1R.

METHODS

Samples from patients with mild AD participating in a longitudinal study in Western Norway (n = 92, 65 [71%] females, mean age 74.8 [range 50-89]) and age- and gender-matched healthy controls (n = 102) were included. Cerebrospinal fluid (CSF) AD biomarkers were assessed in a subgroup of patients. Patients were examined annually, including Mini-Mental State Examination. ELISA was used to measure anti-AT1R in serum. Non-parametric tests were used for statistical calculations and a p <  0.05 was considered significant.

RESULTS

AD patients had significantly higher levels of anti-AT1R compared with healthy controls (10.2 U/mL versus 8.1 U/mL, p = 0.04). This difference was found only in patients without hypertension and diabetes. Anti-AT1R levels correlated with CSF total tau (p = 0.03) and phosphorylated tau (p = 0.03) levels, and inversely with blood pressure in AD (Spearman R -0.277, p = 0.008).

DISCUSSION

AD is associated with increased levels of anti-AT1R, and the antibodies correlated with CSF total, and phosphorylated tau levels. Further research is needed to understand the blood pressure response in AD without hypertension and a potential link between tau and anti-AT1R in AD.

摘要

背景

在心血管疾病中发现了具有激动剂功能的自身抗体。由于血管危险因素与阿尔茨海默病(AD)风险增加相关,我们研究了血管紧张素2 1型受体抗体(抗AT1R)与AD之间的潜在关联。

目的

本研究的主要目的是调查抗AT1R与AD之间的关联。次要目的是调查AD的临床或生物标志物特征与抗AT1R之间的关联。

方法

纳入了参与挪威西部一项纵向研究的轻度AD患者样本(n = 92,65名[71%]女性,平均年龄74.8岁[范围50 - 89岁])以及年龄和性别匹配的健康对照(n = 102)。在部分患者亚组中评估了脑脊液(CSF)AD生物标志物。每年对患者进行检查,包括简易精神状态检查。采用酶联免疫吸附测定(ELISA)法检测血清中的抗AT1R。使用非参数检验进行统计计算,p < 0.05被认为具有统计学意义。

结果

与健康对照相比,AD患者的抗AT1R水平显著更高(10.2 U/mL对8.1 U/mL,p = 0.04)。仅在无高血压和糖尿病的患者中发现了这种差异。抗AT1R水平与CSF总tau(p = 0.03)和磷酸化tau(p = 0.03)水平相关,在AD中与血压呈负相关(斯皮尔曼相关系数R -0.277,p = 0.008)。

讨论

AD与抗AT1R水平升高相关,且这些抗体与CSF总tau及磷酸化tau水平相关。需要进一步研究来了解无高血压的AD患者的血压反应以及AD中tau与抗AT1R之间的潜在联系。

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