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Histology-Compatible MALDI Mass Spectrometry Based Imaging of Neuronal Lipids for Subsequent Immunofluorescent Staining.

Journal article
Authors Ibrahim Kaya
Wojciech Michno
Dimitri Brinet
Yasmine Iacone
Giulia Zanni
Kaj Blennow
Henrik Zetterberg
Jörg Hanrieder
Published in Analytical Chemistry
Volume 89
Issue 8
Pages 4685–4694
ISSN 1520-6882
Publication year 2017
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Department of Chemistry and Molecular Biology
Pages 4685–4694
Language en
Subject categories Neuroscience, Neurochemistry, Neurobiology, Neurosciences, Analytical Chemistry


Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results. We here investigated the histology-compatibility of MALDI-IMS to image neuronal lipids in rodent brain tissue with subsequent immunohistochemistry and fluorescent staining of histological features. This was achieved by sublimation of a low ionization energy matrix compound, 1,5-diaminonapthalene (1,5-DAN), minimizing the number of low-energy laser shots. This yielded improved lipid spectral quality, speed of data acquisition and reduced matrix cluster formation along with preservation of specific histological information at cellular levels. This gentle, histology compatible MALDI IMS protocol also diminished thermal effects and mechanical stress created during nanosecond laser ablation processes that were prominent in subsequent immune-fluorescence staining images but not with classical H&E staining on the same tissue section. Furthermore, this methodology proved to be a powerful strategy for investigating β-amyloid (Aβ) plaque-associated neuronal lipids as exemplified by performing high-resolution MALDI-IMS with subsequent fluorescent amyloid staining in a transgenic mouse model of Alzheimer's disease (tgSwe).

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