Delineating Amyloid Plaque Associated Neuronal Sphingolipids in Transgenic Alzheimer's Disease Mice (tgArcSwe) Using MALDI Imaging Mass Spectrometry
2017 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 8, no 2, 347-355 p.Article in journal (Refereed) Published
The major pathological hallmarks of Alzheimer's disease (AD) are the progressive aggregation and accumulation of beta-amyloid (A beta) and hyperphosphorylated tau protein into neurotoxic deposits. A beta aggregation has been suggested as the critical early inducer, driving the disease progression. However, the factors that promote neurotoxic A beta 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 tissue sections. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used on transgenic Alzheimer's disease mouse (tgArcSwe) brain tissue to investigate the sphingolipid microenvironment of individual A beta plaques and elucidate plaque-associated sphingolipid alterations. Multivariate data analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their lipid chemical profile. This approach revealed sphingolipid species that distinctly located to cortical and hippocampal deposits, whose A beta identity was further verified using fluorescent amyloid staining and immunohistochemistry. Subsequent multivariate statistical analysis of the spectral data revealed significant localization of gangliosides and ceramides species to A beta positive plaques, which was accompanied by distinct local reduction of sulfatides. These plaque-associated changes in sphingolipid levels implicate a functional role of sphingolipid metabolism in A beta plaque pathology and AD pathogenesis. Taken together, the presented data highlight the potential of imaging mass spectrometry as a powerful approach for probing A beta plaque-associated lipid changes underlying AD pathology.
Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2017. Vol. 8, no 2, 347-355 p.
Alzheimer's disease, amyloid-beta plaque pathology, MALDI imaging mass spectrometry, sphingolipids, tgArcSwe
IdentifiersURN: urn:nbn:se:uu:diva-320510DOI: 10.1021/acschemneuro.6b00391ISI: 000394483300017PubMedID: 27984697OAI: oai:DiVA.org:uu-320510DiVA: diva2:1089710
FunderSwedish Research Council, 2014-6447 2012-1593 2013-2546 2013-14002EU, European Research Council, 681712The Dementia Association - The National Association for the Rights of the DementedThe Swedish Brain FoundationStiftelsen Gamla Tjänarinnor