Godoy Juliana Beker, Vialle Ricardo A, Dos Santos Loren, Raittz Roberto T, Wang Yanling, Menon Vilas, De Jager Philip L, Schneider Julie A, Tasaki Shinya, Bennett David A, Guizelini Dieval, Lopes Katia de Paiva
Professional and Technological Education Sector, Federal University of Paraná, Curitiba, Brazil.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
bioRxiv. 2025 Jun 4:2025.06.02.657444. doi: 10.1101/2025.06.02.657444.
Alzheimer's disease (AD) is a complex neurodegenerative condition linked to chronic neuroinflammation. This study investigates the cytokine gene expression profile in cortical tissue samples from elderly individuals with and without AD to identify potential biomarkers and enhance our understanding of disease pathogenesis. Utilizing high-depth RNA sequencing data, we identified a set of cytokines whose expression significantly associated with different aspects of the AD phenotype, including measures of neurofibrillary tangles, amyloid-β deposition, and a person-specific rate of cognitive decline. Single-nucleus transcriptomics data facilitated the identification of specific cell types, such as microglia and oligodendrocytes, that significantly contribute to the inflammatory response in AD. Additionally, we observed a strong correlation between the expression of certain cytokines and genetic risk for the disease. Our findings indicate that cytokine-mediated neuroinflammation plays a vital role in AD progression and that modulating the immune response may offer a promising strategy for developing new therapies.
阿尔茨海默病（AD）是一种与慢性神经炎症相关的复杂神经退行性疾病。本研究调查了患有和未患有AD的老年人皮质组织样本中的细胞因子基因表达谱，以识别潜在的生物标志物，并增进我们对疾病发病机制的理解。利用深度RNA测序数据，我们鉴定出一组细胞因子，其表达与AD表型的不同方面显著相关，包括神经原纤维缠结、淀粉样β蛋白沉积的测量以及个体特异性认知衰退率。单核转录组学数据有助于识别特定的细胞类型，如小胶质细胞和少突胶质细胞，它们对AD中的炎症反应有显著贡献。此外，我们观察到某些细胞因子的表达与该疾病的遗传风险之间存在强烈相关性。我们的研究结果表明，细胞因子介导的神经炎症在AD进展中起着至关重要的作用，调节免疫反应可能为开发新疗法提供一个有前景的策略。
