z-logo
Premium
Dual strategy for reduced signal‐suppression effects in matrix‐assisted laser desorption/ionization mass spectrometry imaging
Author(s) -
Bastrup Joakim,
Birkelund Svend,
Asuni Ayodeji A.,
Volbracht Christiane,
Stensballe Allan
Publication year - 2019
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.8521
Subject(s) - mass spectrometry imaging , chemistry , maldi imaging , laser capture microdissection , mass spectrometry , matrix assisted laser desorption/ionization , trifluoroacetic acid , fragmentation (computing) , matrix (chemical analysis) , desorption , chromatography , biochemistry , gene expression , organic chemistry , adsorption , computer science , gene , operating system
Rationale The molecular complexity of tissue features several signal‐suppression effects which reduce the ionization of analytes significantly and thereby weakens the quality of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS) imaging (MALDI imaging). We report a novel approach in MALDI imaging by reducing signal‐suppression effects for the analysis of beta‐amyloid (Aβ) plaques, one pathological hallmark of Alzheimer's disease (AD). Methods We analyzed Aβ proteoforms from postmortem AD brains and brains from transgenic mice (APPPS1‐21) overexpressing familial AD mutations by combining two techniques: (1) laser capture microdissection (LCM) to accumulate Aβ plaques and (2) phosphoric acid (PA) as additive to the super‐2,5‐dihydroxybenzoic acid matrix. Results LCM and MALDI‐MS enabled tandem mass spectrometric fragmentation of stained Aβ plaques. PA improved the signal‐to‐noise (S/N) ratio, especially of the Aβ1‐42 peptide, by three‐fold compared with the standard matrix additive trifluoroacetic acid. The beneficial effect of the PA matrix additive in MALDI imaging was particularly important for AD brain tissue. We identified several significant differences in Aβ plaque composition from AD compared with APPPS1‐21, underlining the value of reducing signal‐suppressing effects in MALDI imaging. Conclusions We present a novel strategy for overcoming signal‐suppression effects in MALDI imaging of Aβ proteoforms.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here