MALDI Mass Spectrometry Imaging: A Novel Tool for the Identification and Classification of Amyloidosis

Abstract

Amyloidosis is a group of diseases caused by extracellular accumulation of fibrillar polypeptide aggregates. So far, diagnosis is performed by Congo red staining of tissue sections in combination with polarization microscopy. Subsequent identification of the causative protein by immunohistochemistry harbors some difficulties regarding sensitivity and specificity. Mass spectrometry based approaches have been demonstrated to constitute a reliable method to supplement typing of amyloidosis, but still depend on Congo red staining. In the present study, we used matrix‐assisted laser desorption/ionization mass spectrometry imaging coupled with ion mobility separation (MALDI‐IMS MSI) to investigate amyloid deposits in formalin‐fixed and paraffin‐embedded tissue samples. Utilizing a novel peptide filter method, we found a universal peptide signature for amyloidoses. Furthermore, differences in the peptide composition of ALλ and ATTR amyloid were revealed and used to build a reliable classification model. Integrating the peptide filter in MALDI‐IMS MSI analysis, we developed a bioinformatics workflow facilitating the identification and classification of amyloidosis in a less time and sample‐consuming experimental setup. Our findings demonstrate also the feasibility to investigate the amyloid's protein composition, thus paving the way to establish classification models for the diverse types of amyloidoses and to shed further light on the complex process of amyloidogenesis.

Imaging mass spectrometry of gold nanoparticles in a tissue section as an immunohistochemical staining mass probe

“…Matrix‐assisted laser desorption/ionization (MALDI) is a common method to ionize organic molecules with suppressed fragmentation. When applying MALDI to tissue sections, ionization of various molecules such as lipids, metabolites, and drags is possible . The MALDI‐MS setup equipped with a time‐of‐flight spectrometer can detect multiple ions in a single‐step measurement.…”

“…This technique is referred to as “imaging MS” and has a spatial resolution in submillimeter level. Furthermore, by imaging MS, it is feasible to show distribution of multiple biomolecules within tissues . Nevertheless, the interpretation of mass signals is complex because of the hundreds of molecules that desorb from a tissue, all of which are analyzed by the mass spectrometer.…”

“…When applying MALDI to tissue sections, ionization of various molecules such as lipids, metabolites, and drags is possible. [6][7][8][9][10][11][12] The MALDI-MS setup equipped with a time-of-flight spectrometer can detect multiple ions in a single-step measurement. Scanning sample provides a two-dimensional distribution of multiple organic molecules.…”

Proteomics with Mass Spectrometry Imaging: Beyond Amyloid Typing

“…In a recent paper published in Proteomics, Winter and colleagues describe a novel approach based on MALDI–MSI coupled with ion mobility separation and peptide filtering to analyze tissue proteins in systemic amyloidosis samples, with the objectives to identify and classify amyloid deposits . The current approach has relevant distinctive features.…”

“…Identification of amyloid deposits through evaluation of peptide ions from amyloid‐associated proteins: comparison with Congo red staining. See Figure 2 in the article by Winter et al Reproduced with permission . Copyright 2017, Wiley‐VCH.…”