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Novel Trimodal MALDI Imaging Mass Spectrometry (IMS3) at 10 μm Reveals Spatial Lipid and Peptide Correlates Implicated in Aβ Plaque Pathology in Alzheimer’s Disease
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2017-10-04 00:00:00 , DOI: 10.1021/acschemneuro.7b00314
Ibrahim Kaya 1 , Dimitri Brinet 1, 2 , Wojciech Michno 1 , Mehmet Başkurt 1, 3 , Henrik Zetterberg 1, 4, 5, 6 , Kaj Blenow 1, 4 , Jörg Hanrieder 1, 4, 5
Affiliation  

Multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) can provide comprehensive molecular information in situ within the same tissue sections. This is of relevance for studying different brain pathologies such as Alzheimer’s disease (AD), where recent data suggest a critical relevance of colocalizing Aβ peptides and neuronal lipids. We here developed a novel trimodal, high-resolution (10 μm) MALDI imaging MS (IMS) paradigm for negative and positive ion mode lipid analysis and subsequent protein ion imaging on the same tissue section. Matrix sublimation of 1,5-diaminonaphthalene (1,5-DAN) enabled dual polarity lipid MALDI IMS on the same pixel points at high spatial resolutions (10 μm) and with high spectral quality. This was followed by 10 μm resolution protein imaging on the same measurement area, which allowed correlation of lipid signals with protein distribution patterns within distinct cerebellar regions in mouse brain. The demonstrated trimodal imaging strategy (IMS3) was further shown to be an efficient approach for simultaneously probing Aβ plaque-associated lipids and Aβ peptides within the hippocampus of 18 month-old transgenic AD mice (tgArcSwe). Here, IMS3 revealed a strong colocalization of distinct lipid species including ceramides, phosphatidylinositols, sulfatides (Cer 18:0, PI 38:4, ST 24:0) and lysophosphatidylcholines (LPC 16:0, LPC 18:0) with plaque-associated Aβ isoforms (Aβ 1–37, Aβ 1–38, Aβ 1–40). This highlights the potential of IMS3 as an alternative, superior approach to consecutively performed immuno-based Aβ staining strategies. Furthermore, the IMS3 workflow allowed for multimodal in situ MS/MS analysis of both lipids and Aβ peptides. Altogether, the here presented IMS3 approach shows great potential for comprehensive, high-resolution molecular analysis of histological features at cellular length scales with high chemical specificity. It therefore represents a powerful approach for probing the complex molecular pathology of, e.g., neurodegenerative diseases that are characterized by neurotoxic protein aggregation.

中文翻译:

新型三峰MALDI成像质谱(IMS3)的10μm揭示了阿尔茨海默氏病Aβ斑块病理学中所涉及的空间脂质和多肽相关性

使用基质辅助激光解吸/电离质谱(MALDI-MS)进行的多峰化学成像可在同一组织切片中提供原位的全面分子信息。这与研究不同的脑部疾病(例如阿尔茨海默氏病(AD))具有相关性,最近的数据表明,共定位Aβ肽和神经元脂质具有至关重要的相关性。我们在这里开发了一种新颖的三峰,高分辨率(10μm)MALDI成像MS(IMS)范例,用于负离子和正离子模式脂质分析以及随后在同一组织切片上的蛋白质离子成像。1,5-二氨基萘(1,5-DAN)的基质升华可在同一像素点上以高空间分辨率(10μm)和高光谱质量实现双极性脂质MALDI IMS。随后在相同的测量区域上进行10μm分辨率的蛋白质成像,从而使脂质信号与小鼠脑中不同小脑区域内的蛋白质分布模式相关。进一步证明了证明的三峰成像策略(IMS3)是一种有效的方法,可同时探测18个月大转基因AD小鼠(tgArcSwe)海马中的Aβ斑块相关脂质和Aβ肽。在这里,IMS3揭示了不同脂质种类的强烈共定位,包括神经酰胺,磷脂酰肌醇,硫化物(Cer 18:0,PI 38:4,ST 24:0)和溶血磷脂酰胆碱(LPC 16:0,LPC 18:0)与斑块相关Aβ亚型(Aβ1–37,Aβ1–38,Aβ1–40)。这突显了IMS3作为替代的,优于连续进行的基于免疫的Aβ染色策略的方法的潜力。此外,IMS3工作流程允许对脂质和Aβ肽进行多峰原位MS / MS分析。总之,此处介绍的IMS3方法显示了具有高度化学特异性的,在细胞长度尺度上进行组织学特征的全面,高分辨率分子分析的巨大潜力。因此,它代表了一种探索诸如以神经毒性蛋白聚集为特征的神经退行性疾病的复杂分子病理学的有力方法。
更新日期:2017-10-04
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