Senile plaques formed by aggregated
amyloid β
peptides are one of the major pathological hallmarks of
Alzheimer's disease (AD) which have been suggested to be the primary influence triggering the AD pathogenesis and the rest of the disease process. However, neurotoxic Aβ aggregation and progression are associated with a wide range of enigmatic biochemical, biophysical and genetic processes. MALDI imaging mass spectrometry (IMS) is a label-free method to elucidate the spatial distribution patterns of intact molecules in biological tissue sections. In this communication, we utilized multimodal MALDI-IMS analysis on 18 month old transgenic AD mice (tgArcSwe) brain tissue sections to enhance molecular information correlated to individual
amyloid aggregates on the very same tissue section. Dual polarity MALDI-IMS analysis of
lipids on the same pixel points revealed high throughput
lipid molecular information including
sphingolipids,
phospholipids, and
lysophospholipids which can be correlated to the ion images of individual
amyloid β
peptide isoforms at high spatial resolutions (10 μm). Further, multivariate image analysis was applied in order to probe the multimodal MALDI-IMS data in an unbiased way which verified the correlative accumulations of
lipid species with dual polarity and Aβ
peptides. This was followed by the
lipid fragmentation obtained directly on plaque aggregates at higher
laser pulse energies which provided tandem MS information useful for structural elucidation of several
lipid species. Majority of the
amyloid plaque-associated alterations of
lipid species are for the first time reported here. The significance of this technique is that it allows correlating the biological discussion of all detected plaque-associated molecules to the very same individual
amyloid plaques which can give novel insights into the molecular pathology of even a single
amyloid plaque microenvironment in a specific brain region. Therefore, this allowed us to interpret the possible roles of
lipids and
amyloid peptides in
amyloid plaque-associated pathological events such as focal
demyelination, autophagic/lysosomal dysfunction,
astrogliosis,
inflammation, oxidative stress, and cell death.