Probing Amyloid-β Pathology in transgenic Alzheimer's disease (tgArcSwe) mice using MALDI Imaging Mass Spectrometry

• Published in: Journal of Neurochemistry
• Main Authors: Carlred, Louise M, Michno, W., Kaya, I., Sjövall, Peter, Syvanen, S., Hanrieder, Jörg
• Language: unknown
• Published: 2016
• Subjects: Biochemistry and Molecular Biology; Analytical Chemistry; Neurosciences; Cell and Molecular Biology; Alzheimer's disease; MALDI imaging; amyloid beta; dementia; Arctic
• Online Access: https://doi.org/10.1111/jnc.13645; https://research.chalmers.se/en/publication/235423

The pathological mechanisms underlying Alzheimer's disease (AD) are still not understood. The disease pathology is characterized by accumulation and aggregation of amyloid-β (Aβ) peptides into extracellular plaques, however the factors that promote neurotoxic Aβ aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides and proteins in biological tissues. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) based imaging was used to study Aβ deposition in transgenic mouse brain tissue and to elucidate the plaque associated chemical microenvironment. The imaging experiments were performed in brain sections of transgenic Alzheimer's disease mice carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe). Multivariate image analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their chemical identity. This include cortical and hippocampal Aβ deposits, whose amyloid peptide content was further verified using immunohistochemistry and laser micro dissection followed by MALDI MS analysis. Subsequent statistical analysis on spectral data of regions of interest (ROI) revealed brain region specific differences in Aβ peptide aggregation. Moreover, other plaque associated protein species were identified including macrophage migration inhibitory factor (MIF) suggesting neuroinflammatory processes and glial cell reactivity to be involved in AD pathology. The presented data further highlight the potential of IMS as powerful approach in neuropathology.