Probing amyloid-β pathology in transgenic Alzheimer's disease (tgArcSwe) mice using MALDI imaging mass spectrometry
2016 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 138, no 3, 469-478 p.Article in journal (Refereed) Published
The pathological mechanisms underlying Alzheimer's disease (AD) are still not understood. The disease pathology is characterized by the accumulation and aggregation of amyloid- (A) peptides into extracellular plaques, however the factors that promote neurotoxic A 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 A 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 A deposits, whose amyloid peptide content was further verified using immunohistochemistry and laser microdissection followed by MALDI MS analysis. Subsequent statistical analysis on spectral data of regions of interest revealed brain region-specific differences in A peptide aggregation. Moreover, other plaque-associated protein species were identified including macrophage migration inhibitory factor suggesting neuroinflammatory processes and glial cell reactivity to be involved in AD pathology. The presented data further highlight the potential of IMS as a powerful approach in neuropathology.
Place, publisher, year, edition, pages
2016. Vol. 138, no 3, 469-478 p.
Alzheimers's disease, amyloid-beta plaques, dementia, MALDI imaging mass spectrometry, tgArcSwe
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-303106DOI: 10.1111/jnc.13645ISI: 000380914000010PubMedID: 27115712OAI: oai:DiVA.org:uu-303106DiVA: diva2:974913
FunderSwedish Research Council, 2014-6447, 2015-04199, 2012-1593Stiftelsen Gamla Tjänarinnor