阿尔茨海默病在离体人小胶质细胞中的转录景观，这一成果由美国西奈山伊坎医学院Panos Roussos研究组经过不懈努力而取得。2025年8月4日，国际知名学术期刊《自然—神经科学》发表了这一成果。

课题组对189名人类死后大脑的初级小胶质细胞进行了转录分析，其中包括58名健康的老年人和131名具有一系列疾病表型的患者，例如63名代表阿尔茨海默病的完整临床和病理谱的患者。该研究组确定了与多种AD表型相关的变化，捕获了痴呆和神经病理病变的严重程度。转录水平分析鉴定了具有异质异构体和AD表型的其他基因。该研究组发现了AD中基因协调的变化，共表达模块的失调以及具有不同基因表达模式的疾病亚型。

综上所述，这些数据进一步加深了他们对小胶质细胞在阿尔茨海默病生物学中的关键作用的理解，并提名了治疗干预的候选药物。

据了解，小胶质细胞是大脑的常驻免疫细胞，与阿尔茨海默病（AD）和其他疾病的病因有关。然而，在整个疾病过程中调节其功能的细胞和分子过程尚不清楚。

附：英文原文

Title: Alzheimer’s disease transcriptional landscape in ex vivo human microglia

Author: Kosoy, Roman, Fullard, John F., Bendl, Jaroslav, Kleopoulos, Steven P., Shao, Zhiping, Argyriou, Stathis, Mathur, Deepika, Psychogyiou, Konstantina, Malakates, Periklis, Vicari, James, Ma, Yixuan, Humphrey, Jack, Brophy, Erica, Raj, Towfique, Katsel, Pavel, Voloudakis, Georgios, Lee, Donghoon, Bennett, David A., Haroutunian, Vahram, Hoffman, Gabriel E., Roussos, Panos

Issue&Volume: 2025-08-04

Abstract: Microglia are resident immune cells of the brain and are implicated in the etiology of Alzheimer’s disease (AD) and other diseases. Yet the cellular and molecular processes regulating their function throughout the course of the disease are poorly understood. Here, we present a transcriptional analysis of primary microglia from 189 human postmortem brains, including 58 healthy aging individuals and 131 with a range of disease phenotypes, such as 63 patients representing the full clinical and pathological spectra of AD. We identified changes associated with multiple AD phenotypes, capturing the severity of dementia and neuropathological lesions. Transcript-level analyses identified additional genes with heterogeneous isoform usage and AD phenotypes. We identified changes in gene–gene coordination in AD, dysregulation of coexpression modules and disease subtypes with distinct gene expression patterns. Taken together, these data further our understanding of the key role that microglia have in AD biology and nominate candidates for therapeutic intervention.

DOI: 10.1038/s41593-025-02020-2

Source: https://www.nature.com/articles/s41593-025-02020-2