Chaudhuri Soumilee, Cho Minyoung, Stumpff Julia C, Bice Paula J, İş Özkan, Ertekin-Taner Nilüfer, Saykin Andrew J, Nho Kwangsik
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Mol Neurodegener. 2025 Jan 29;20(1):12. doi: 10.1186/s13024-025-00798-0.
Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in high throughput single-cell transcriptomics technology have enabled the study of the human brain vasculature at an unprecedented depth. Additionally, the understudied niche of cerebrovascular cells, such as endothelial and mural cells, and their subtypes have been scrutinized for understanding cellular and transcriptional heterogeneity in AD. Here, we provide an overview of rich transcriptional signatures derived from recent single-cell and single-nucleus transcriptomic studies of human brain vascular cells and their implications for targeted therapy for AD. We conducted an in-depth literature search using Medline and Covidence to identify pertinent AD studies that utilized single-cell technologies in human post-mortem brain tissue by focusing on understanding the transcriptional differences in cerebrovascular cell types and subtypes in AD and cognitively normal older adults. We also discuss impaired cellular crosstalk between vascular cells and neuroglial units, as well as astrocytes in AD. Additionally, we contextualize the findings from single-cell studies of distinct endothelial cells, smooth muscle cells, fibroblasts, and pericytes in the human AD brain and highlight pathways for potential therapeutic interventions as a concerted multi-omic effort with spatial transcriptomics technology, neuroimaging, and neuropathology. Overall, we provide a detailed account of the vascular cell-specific transcriptional signatures in AD and their crucial cellular crosstalk with the neuroglial unit.
阿尔茨海默病（AD）是一种使人衰弱的神经退行性疾病，其特征是严重的神经血管功能障碍以及脑血管系统中显著的细胞特异性改变。高通量单细胞转录组学技术的最新进展使人们能够以前所未有的深度研究人类脑血管系统。此外，脑血管细胞（如内皮细胞和平滑肌细胞）及其亚型这一研究较少的生态位已被仔细研究，以了解AD中的细胞和转录异质性。在此，我们概述了源自近期人类脑血管细胞单细胞和单细胞核转录组学研究的丰富转录特征及其对AD靶向治疗的意义。我们使用Medline和Covidence进行了深入的文献检索，以识别通过关注AD和认知正常的老年人脑血管细胞类型和亚型的转录差异，在人类死后脑组织中利用单细胞技术的相关AD研究。我们还讨论了AD中血管细胞与神经胶质单元以及星形胶质细胞之间受损的细胞间通讯。此外，我们将人类AD大脑中不同内皮细胞、平滑肌细胞、成纤维细胞和周细胞的单细胞研究结果置于背景中，并强调作为与空间转录组学技术、神经影像学和神经病理学协同的多组学努力的潜在治疗干预途径。总体而言，我们详细阐述了AD中血管细胞特异性转录特征及其与神经胶质单元至关重要的细胞间通讯。
