Single-synapse analyses of Alzheimer’s disease implicate pathologic tau, DJ1, CD47, and ApoE

Synaptic molecular characterization is limited for Alzheimer’s disease (AD). Our newly invented mass cytometry-based method, Synaptometry by Time of Flight (SynTOF), was used to measure 38 antibody probes in approximately 17 million single-synapse events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), non-human primates (NHP), and PS/APP mice. Synaptic molecular integrity in humans and NHP was similar. Although not detected in human synapses, Aβ was in PS/APP mice single-synapse events. Clustering and pattern identification of human synapses showed expected disease-specific differences, like increased hippocampal pathologic tau in AD and reduced caudate dopamine transporter in LBD, and revealed novel findings including increased hippocampal CD47 and lowered DJ1 in AD and higher ApoE in AD with dementia. Our results were independently supported by multiplex ion beam imaging of intact tissue. This highlights the higher depth and breadth of insight o..., The dataset was collected using mass cytometry at The Human Immune Monitoring Center (HIMC) and multiplexed ion beam imaging by time of flight (MIBI-TOF) at Stanford University in 2019-2020 and 2020, respectively. The single-synapse data has been processed by arcsinh transformed with a cofactor of 5 to produce the results published in Science Advances, where a detailed experimental method and preprocessing can be found., The readme file contains an explanation of each of the metadata of each file (both SynTOF and MIBI-TOF) as well as the column and value descriptions. Information on how the measurements were done can be found in the associated manuscript referenced above. We have also attached scripts we used to generate the results presented in the paper. The explanation of each of the script file is written in readme-files within the zip folder.阿尔茨海默病(Alzheimer’s disease, AD)的突触分子特征研究仍存在较大局限。本团队新近研发的基于质谱流式细胞术(mass cytometry)的方法——飞行时间突触计量法(Synaptometry by Time of Flight, SynTOF)，被用于检测约1700万个单突触事件中的38种抗体探针，样本涵盖无病理改变的人脑组织、纯AD或路易体病(Lewy body disease, LBD)患者脑组织、非人灵长类(non-human primates, NHP)以及PS/APP小鼠脑组织。人与非人灵长类的突触分子完整性水平相近。尽管在人类突触中未检测到Aβ，但该蛋白在PS/APP小鼠的单突触事件中有所检出。对人类突触进行聚类与模式识别分析，结果呈现出预期的疾病特异性差异：例如AD患者海马区病理性tau蛋白水平升高，LBD患者尾状核多巴胺转运体表达降低；同时还揭示了多项新发现，包括AD患者海马区CD47水平升高、DJ1水平降低，以及伴痴呆的AD患者体内ApoE水平升高。本研究结果得到了完整组织多重离子束成像(multiplex ion beam imaging)的独立验证。这凸显了本研究在认知深度与广度上的优势…… 该数据集分别于2019-2020年及2020年，由斯坦福大学人类免疫监测中心(The Human Immune Monitoring Center, HIMC)利用质谱流式细胞术，以及斯坦福大学的飞行时间多重离子束成像(multiplexed ion beam imaging by time of flight, MIBI-TOF)技术采集完成。单突触数据已通过以5为辅助因子的反正双曲正弦变换(arcsinh transformed)进行预处理，以生成发表于《Science Advances》的研究结果，该期刊中包含详细的实验方法与预处理流程说明。 README文件对所有文件（包括SynTOF与MIBI-TOF相关文件）的元数据、各列及其取值均进行了解释。关于实验测量的具体细节，可参阅前文提及的相关研究论文。本数据集同时附带了用于复现论文中研究结果的代码脚本，所有脚本文件的说明文档均收录于压缩包内的README文件中。