Lipid imaging of Alzheimer's disease pathology.
Lipid imaging of Alzheimer's disease pathology.
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阿尔茨海默病病理学的脂质成像。
DOI：
10.1111/jnc.16079
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发表时间：
2024
影响因子：
4.7
通讯作者：
Hanrieder,Jörg
中科院分区：
文献类型：
--
作者：
Hanrieder,Jörg
阿尔茨海默病 (AD) 影响 65 岁以上老人中八分之一的患病率，并带来了巨大的社会挑战。 AD 病理学的特点是大脑中形成 β-淀粉样斑块和 Tau 蛋白缠结。虽然一些针对β淀粉样蛋白的疾病缓解疗法正在出现，但这种疾病发病机制背后的确切事件链仍不清楚。长期以来，脑脂质一直与 AD 病理有关，但其在 AD 发病机制中的作用尚未完全解决。质谱成像（MSI）的重大进步使得能够在低微米尺度上详细描述生物组织中的空间脂质调节。在本期中，黄等人。使用基于解吸电喷雾电离 (DESI) 的 MSI 与其他空间技术（例如相关蛋白质特征的成像质量流式细胞仪）相结合，解析人类 AD 大脑和遗传小鼠模型中的空间脂质模式。这些空间多组学实验确定了与斑块相关的脂质调节，这些调节依赖于小鼠模型和人脑中斑块病理进展。在这些脂质种类中，特别是促炎性溶血磷脂通过脂质传感表面受体与聚集的 Aβ 和小胶质细胞活化相互作用，与 AD 病理有关。总之，这项研究进一步深入了解了脑脂质稳态如何与进展的 AD 病理学相关，从而凸显了基于 MSI 的空间脂质组学作为生物医学研究的新兴空间生物学技术的潜力。
Alzheimer's disease (AD) affects one in eight individuals over 65 and poses an immense societal challenge. AD pathology is characterized by the formation of beta‐amyloid plaques and Tau tangles in the brain. While some disease‐modifying treatments targeting beta‐amyloid are emerging, the exact chain of events underlying the pathogenesis of this disease remains unclear. Brain lipids have long been implicated in AD pathology, though their role in AD pathogenesis remains not fully resolved. Significant advancements in mass spectrometry imaging (MSI) allow to detail spatial lipid regulations in biological tissues at the low um scale. In this issue, Huang et al. resolve spatial lipid patterns in human AD brain and genetic mouse models using desorption electrospray ionization (DESI)‐based MSI integrated with other spatial techniques such as imaging mass cytometry of correlative protein signatures. Those spatial multiomics experiments identify plaque‐associated lipid regulations that are dependent on progressing plaque pathology in both mouse models and the human brain. Of those lipid species, particularly pro‐inflammatory lysophospholipids have been implicated in AD pathology through their interaction with both aggregating Aβ and microglial activation through lipid sensing surface receptors. Together, this study provides further insight into how brain lipid homeostasis is linked to progressing AD pathology, and thereby highlights the potential of MSI‐based spatial lipidomics as an emerging spatial biology technology for biomedical research.