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Title: Novel trimodal MALDI imaging mass spectrometry (IMS3) at 10 µm reveals spatial lipid and peptide correlates implicated in Aß plaque pathology in alzheimer's disease
Authors: Kaya, İbrahim
Brinet, Dimitri
Michno, Wojciech
Başkurt, Mehmet
Zetterberg, Henrik
Blenow, Kaj
Hanrieder, Jo¨rg
Keywords: Alzheimer's disease
Neuronal lipids
Plaque pathology
Aβ peptides
Amyloid beta protein
MALDI imaging
Issue Date: Dec-2017
Publisher: American Chemical Society
Source: Kaya, İ., Brinet, D., Michno, W., Başkurt, M., Zetterberg, H., Blenow, K., and Hanrieder, J. (2017). 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, 8(12), 2778-2790. doi:10.1021/acschemneuro.7b00314
Abstract: 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.
ISSN: 1948-7193
Appears in Collections:Chemistry / Kimya
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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