阿尔茨海默病中的嗅裂活检：一扇通向临床前病理生物学的新兴神经免疫窗口

文献信息

中文摘要

背景： 嗅觉功能障碍是阿尔茨海默病（AD）的一种早期非认知特征，但嗅觉损害传统上主要被用作行为标志物。本综述探讨了将嗅裂作为可获取的活体神经元、上皮细胞、祖细胞和免疫细胞来源以研究AD病理生物学的这一新兴用途。方法：组织病理学和患者来源培养研究已报道嗅组织中的淀粉样蛋白β、tau、氧化应激、线粒体、生物金属和转录异常。结果：较新的内镜引导下刷取采样结合单细胞谱分析已识别出活化的记忆CD8 T细胞状态、炎症性髓系程序以及神经元代谢改变，包括在脑脊液淀粉样蛋白生物标志物异常但认知未受损的个体中。结论：这些发现支持将嗅裂采样作为研究早期神经免疫变化的研究平台，但当前证据基于规模较小、且大多为横断面的队列，尚不能确立疾病特异性、因果关系或预后价值。在临床转化之前，需要开展纵向多中心研究，将嗅组织谱分析与已确立的液体、影像、遗传、认知和嗅觉生物标志物相结合。

英文摘要

Olfactory dysfunction is an early non-cognitive feature of Alzheimer's disease (AD), but smell impairment has traditionally been used mainly as a behavioral marker. This review examines the emerging use of the olfactory cleft as an accessible source of living neuronal, epithelial, progenitor, and immune cells for studying AD pathobiology. Histopathological and patient-derived culture studies have reported amyloid-β, tau, oxidative-stress, mitochondrial, biometal, and transcriptional abnormalities in olfactory tissue. More recent endoscopically guided brush sampling with single-cell profiling has identified activated memory CD8 T-cell states, inflammatory myeloid programs, and neuronal metabolic changes, including in cognitively unimpaired individuals with abnormal cerebrospinal-fluid amyloid biomarkers. These findings support olfactory-cleft sampling as a research platform for investigating early neural-immune changes, but current evidence is based on small, largely cross-sectional cohorts and does not establish disease specificity, causality, or prognostic utility. Longitudinal multicenter studies integrating olfactory-tissue profiling with established fluid, imaging, genetic, cognitive, and olfactory biomarkers are required before clinical translation.