The anti-inflammatory cytokine interferon-gamma as a potential therapeutic target of Alzheimer’s disease: a retrospective observational study

Li, Weiqi1; Huang, Xudong2; Pang, Xinping3; Sun, Yue1; Zeng, Zihang1; Zheng, Pengtao1; Gao, Chonghao1; Pang, Chaoyang1,*

1 College of Computer Science, Sichuan Normal University, Chengdu, Sichuan Province, China

2 Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

3 School of Science, Xi’an Jiaotong-Liverpool University, Suzhou, Jiangsu Province, China

*Correspondence to: Chaoyang Pang, PhD, cypang@sicnu.edu.cn.

Abstract

The age-related neurodegenerative disease Alzheimer’s disease is characterized by progressive cognitive decline and neurodegeneration and is often accompanied by inflammation within the central nervous system. This study investigated the role of interferon-gamma, an anti-inflammatory cytokine, in Alzheimer’s disease pathogenesis. Our findings highlight three critical insights: first, there was a significant reduction in interferon-gamma expression at the early stages of Alzheimer’s disease, suggesting an initial impairment in immune function. Second, we identified a novel correlation between the expression levels of interferon-gamma and its receptors, which may indicate a mechanism through which interferon-gamma signaling is altered in Alzheimer’s disease. Third, we observed an increase in entropy and determinant values for interferon-gamma and its receptors, suggesting that systemic dysregulation likely contributes to disease progression. Our study underscores the pivotal role of interferon-gamma in Alzheimer’s disease and highlights its potential as a therapeutic target.

干扰素-γ是阿尔茨海默病的潜在治疗靶点：观察性回顾研究

摘要

与年龄相关的神经退行性疾病阿尔茨海默病的特征是进行性认知功能衰退和神经退行性变，通常伴有中枢神经系统内的炎症。此研究探讨了抗炎细胞因干扰素γ在阿尔茨海默病发病机制中的作用。研究结果凸显了三个重要的见解：首先，在阿尔茨海默病的早期阶段，干扰素γ的表达显著减少，这表明免疫功能最初受到了损害。其次，干扰素γ 的表达水平与其受体之间存在新的相关性，这可能表明干扰素γ 信号在阿尔茨海默病中发生改变的机制。第三，干扰素γ及其受体的熵值和行列式值增加，这表明系统性失调可能导致疾病进展。这些结果表明，干扰素γ在阿尔茨海默病中的关键作用，并突出了其作为治疗靶点的潜力。