阿尔茨海默病患者异常细胞免疫与磁共振波谱变化的相关性。

Correlation between abnormal cellular immune and changes of magnetic resonance spectroscopy in patients with Alzheimer's disease.

机构信息

Department of Neurology, The Third Affiliated Hospital of Guizhou Medical University, Duyun, 558099, China; Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.

Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou Medical University, Guiyang, 550004, China; Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, China.

出版信息

Neurochem Int. 2024 Jun;176:105737. doi: 10.1016/j.neuint.2024.105737. Epub 2024 Apr 9.

DOI:10.1016/j.neuint.2024.105737

PMID:38599243

Abstract

BACKGROUND

Evidence from previous studies indicates that neuroinflammation contributes to the onset of Alzheimer's Disease (AD). Moreover, cellular dysfunction is induced by impaired signaling of neurotransmitters. This study aimed to explore the correlation between cellular immune dysfunction and neurotransmitter changes through cranial Magnetic Resonance Spectroscopy (MRS) in AD patients.

METHODS

Here, 32 AD, 40 Vascular Dementia (VD), and 35 Non-Dementia Elderly Control (NDE) cases were enrolled. Flow cytometry was performed to characterize lymphocyte subsets in plasma samples. The IL-1β and Caspase-1 levels were detected by ELISA. The NLRP3 expression level was measured by Western Blot (WB). The equivalence of N-acetylaspartate (NAA), Creatine (Cr), Choline (Cho), and Inositol (MI) in bilateral hippocampi of patients was examined by MRS. The association of NAA/Cr or MI/Cr ratios with the proportion of T lymphocyte subsets or NK cell subsets was determined through single-factor correlation analysis.

RESULTS

The proportion of T lymphocyte subsets was significantly lower in the AD group than in the NDE group (P < 0.01). On the other hand, the Caspase-1, NLRP3, and IL-1β protein expression levels were significantly higher in the AD group than in the other groups. Further analysis showed that the NAA/Cr ratio was lower in the AD group than in the NDE group. Additionally, a significant positive correlation was found between the NAA/Cr ratio and the MMSE score (r = 0.81, P < 0.01). Moreover, a significant positive correlation was observed between the NAA/Cr and T lymphocyte ratios. The NAA/Cr ratio was significantly negatively correlated with the proportion of NK cells in the blood (r = －0.83, P < 0.01). A significant negative correlation was also recorded between the MI/Cr and T cell ratios in blood samples.

CONCLUSIONS

Impaired cellular immune dysfunction in AD patients was significantly correlated with abnormal MRS. Neuroimmune dysfunction may contribute to the pathogenesis of AD and alter the metabolism of neurotransmitters such as aspartic acid and MI in the brains of AD patients.

TRIAL REGISTRATION

Not applicable.

摘要

背景

先前的研究证据表明，神经炎症会导致阿尔茨海默病（AD）的发生。此外，神经递质信号转导受损会导致细胞功能障碍。本研究旨在通过磁共振波谱（MRS）探索 AD 患者的细胞免疫功能障碍与神经递质变化之间的相关性。

方法

本研究纳入了 32 例 AD、40 例血管性痴呆（VD）和 35 例非痴呆老年对照组（NDE）患者。采用流式细胞术分析血浆样本中的淋巴细胞亚群。采用 ELISA 法检测白细胞介素-1β（IL-1β）和半胱氨酸天冬氨酸蛋白酶-1（Caspase-1）水平。采用 Western blot（WB）法检测 NLRP3 表达水平。采用 MRS 检测双侧海马区 N-乙酰天冬氨酸（NAA）、肌酸（Cr）、胆碱（Cho）和肌醇（MI）的含量。通过单因素相关分析，确定 NAA/Cr 或 MI/Cr 比值与 T 淋巴细胞亚群或 NK 细胞亚群比例的相关性。

结果

AD 组 T 淋巴细胞亚群比例明显低于 NDE 组（P<0.01）。AD 组的 Caspase-1、NLRP3 和 IL-1β 蛋白表达水平明显高于其他组。进一步分析显示，AD 组的 NAA/Cr 比值低于 NDE 组。此外，NAA/Cr 比值与 MMSE 评分呈显著正相关（r=0.81，P<0.01）。同时，NAA/Cr 比值与 T 淋巴细胞比值呈显著正相关。NAA/Cr 比值与血液中 NK 细胞比例呈显著负相关（r=-0.83，P<0.01）。血液样本中 MI/Cr 与 T 细胞比值也呈显著负相关。