以色列魏茨曼科学研究所Michal Schwartz等研究人员，合作鉴定出衰老和阿尔茨海默病模型小鼠大脑中衰老且表达TREM2的小胶质细胞。该项研究成果于2024年4月18日在线发表在《自然—神经科学》杂志上。

研究人员表示，AD和一般痴呆症是与年龄有关的疾病，有多种诱因，包括脑部炎症。小胶质细胞，特别是那些表达AD风险基因TREM2的小胶质细胞，被认为是AD的重要参与者，但它们对病理学的确切贡献仍不清楚。

附：英文原文

Title: Identification of senescent, TREM2-expressing microglia in aging and Alzheimer’s disease model mouse brain

Author: Rachmian, Noa, Medina, Sedi, Cherqui, Ulysse, Akiva, Hagay, Deitch, Daniel, Edilbi, Dunya, Croese, Tommaso, Salame, Tomer Meir, Ramos, Javier Maria Peralta, Cahalon, Liora, Krizhanovsky, Valery, Schwartz, Michal

Issue&Volume: 2024-04-18

Abstract: Alzheimer’s disease (AD) and dementia in general are age-related diseases with multiple contributing factors, including brain inflammation. Microglia, and specifically those expressing the AD risk gene TREM2, are considered important players in AD, but their exact contribution to pathology remains unclear. In this study, using high-throughput mass cytometry in the 5×FAD mouse model of amyloidosis, we identified senescent microglia that express high levels of TREM2 but also exhibit a distinct signature from TREM2-dependent disease-associated microglia (DAM). This senescent microglial protein signature was found in various mouse models that show cognitive decline, including aging, amyloidosis and tauopathy. TREM2-null mice had fewer microglia with a senescent signature. Treating 5×FAD mice with the senolytic BCL2 family inhibitor ABT-737 reduced senescent microglia, but not the DAM population, and this was accompanied by improved cognition and reduced brain inflammation. Our results suggest a dual and opposite involvement of TREM2 in microglial states, which must be considered when contemplating TREM2 as a therapeutic target in AD.

DOI: 10.1038/s41593-024-01620-8

Source: https://www.nature.com/articles/s41593-024-01620-8