小柯机器人

美国哥伦比亚大学Philip L. De Jager、Vilas Menon和以色列耶路撒冷希伯来大学Naomi Habib研究组合作的研究发现，在老年人和阿尔茨海默病（AD）人的大脑中多细胞群落受到干扰。相关论文于2023年6月19日发表在《自然—神经科学》杂志上。

研究人员通过对具有一系列临床病理特征的24个个体进行单核RNA测序，重塑衰老额叶皮层的高分辨率细胞图，来探究AD中不同细胞类型及其相互作用。研究使用该图谱推断了批量RNA测序分析的638个个体新皮质细胞的结构，提供了在统计学上识别稳定关联的样本量。研究人员发现了与AD相关的各种细胞群，包括生长抑素抑制性神经元亚型和少突胶质细胞状态。

研究进一步确定了多细胞群落网络，每个群落由神经元、神经胶质和内皮细胞的协调亚群组成，研究人员发现其中两个群落在AD中发生了改变。最后，研究人员通过使用中介分析确定了可能导致认知能力下降细胞变化的优先级。因此，对衰老新皮层解构的解析为评估AD和痴呆背后的细胞微环境提供了基础。

研究人员表示，在阿尔茨海默病中不同细胞类型及其相互作用一直是一个复杂而开放的问题。

附：英文原文

Title: Multicellular communities are perturbed in the aging human brain and Alzheimer’s disease

Author: Cain, Anael, Taga, Mariko, McCabe, Cristin, Green, Gilad S., Hekselman, Idan, White, Charles C., Lee, Dylan I., Gaur, Pallavi, Rozenblatt-Rosen, Orit, Zhang, Feng, Yeger-Lotem, Esti, Bennett, David A., Yang, Hyun-Sik, Regev, Aviv, Menon, Vilas, Habib, Naomi, De Jager, Philip L.

Issue&Volume: 2023-06-19

Abstract: The role of different cell types and their interactions in Alzheimer’s disease (AD) is a complex and open question. Here, we pursued this question by assembling a high-resolution cellular map of the aging frontal cortex using single-nucleus RNA sequencing of 24 individuals with a range of clinicopathologic characteristics. We used this map to infer the neocortical cellular architecture of 638 individuals profiled by bulk RNA sequencing, providing the sample size necessary for identifying statistically robust associations. We uncovered diverse cell populations associated with AD, including a somatostatin inhibitory neuronal subtype and oligodendroglial states. We further identified a network of multicellular communities, each composed of coordinated subpopulations of neuronal, glial and endothelial cells, and we found that two of these communities are altered in AD. Finally, we used mediation analyses to prioritize cellular changes that might contribute to cognitive decline. Thus, our deconstruction of the aging neocortex provides a roadmap for evaluating the cellular microenvironments underlying AD and dementia.

DOI: 10.1038/s41593-023-01356-x

Source: https://www.nature.com/articles/s41593-023-01356-x

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex