Alvarado Chelsea X, Weller Cory A, Johnson Nicholas, Leonard Hampton L, Singleton Andrew B, Reed Xylena, Blauewendraat Cornelis, Nalls Mike
Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
medRxiv. 2023 Jul 1:2023.06.30.23292084. doi: 10.1101/2023.06.30.23292084.
Single cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression. To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single cell sequencing data, and bulk expression studies in a diverse series of brain region tissues. We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Diseases. Subsequently, we identified the major role of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis.
单细胞RNA测序为阐明疾病的复杂基础打开了一扇窗口，尤其是在量化组织和细胞类型特异性基因表达的相关性方面。为了确定对整个神经退行性疾病谱系中治疗靶点开发至关重要的细胞类型和基因，我们利用了全基因组关联研究、近期的单细胞测序数据以及一系列不同脑区组织中的大量表达研究。我们能够在三种主要神经退行性疾病（阿尔茨海默病、肌萎缩侧索硬化症和帕金森病）的大脑中识别出与免疫相关的重要细胞类型。随后，我们确定了30个精细定位位点的主要作用，这些位点涉及多个神经退行性疾病及其发病机制中的7个基因。
