{"title":"Multiplex imaging of amyloid-β plaques dynamics in living brains with quinoline-malononitrile-based probes","authors":"Jianfeng Dai, Weijun Wei, Chenxu Yan, Ding-Kun Ji, Caiqi Liu, Jialiang Huang, Chenyi Liang, Jianjun Liu, Zhiqian Guo, Wei-Hong Zhu","doi":"10.1038/s41551-025-01392-x","DOIUrl":null,"url":null,"abstract":"<p>The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer’s disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via near-infrared fluorescence imaging, magnetic resonance imaging, positron emission tomography and computed tomography. QMFluor probes are permeable to the blood–brain barrier, and, upon systematic injection, enable real-time magnetic resonance imaging and positron emission tomography–computed tomography imaging of the Aβ biodistribution in the hippocampus and cerebral cortex, and accurately differentiate the brains of living Alzheimer’s disease mouse models from wild-type controls. We further demonstrate the ability of QMFluor probes to reach the brain after intravenous injection in a large animal model. This strategy expands the toolbox of probes for in vivo visualization of amyloids in Alzheimer’s disease pathological analysis, drug screening and clinical applications.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"117 1","pages":""},"PeriodicalIF":26.8000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1038/s41551-025-01392-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer’s disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via near-infrared fluorescence imaging, magnetic resonance imaging, positron emission tomography and computed tomography. QMFluor probes are permeable to the blood–brain barrier, and, upon systematic injection, enable real-time magnetic resonance imaging and positron emission tomography–computed tomography imaging of the Aβ biodistribution in the hippocampus and cerebral cortex, and accurately differentiate the brains of living Alzheimer’s disease mouse models from wild-type controls. We further demonstrate the ability of QMFluor probes to reach the brain after intravenous injection in a large animal model. This strategy expands the toolbox of probes for in vivo visualization of amyloids in Alzheimer’s disease pathological analysis, drug screening and clinical applications.
期刊介绍:
Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.