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Spatial Lipidomics Reveals Region and Long Chain Base Specific Accumulations of Monosialogangliosides in Amyloid Plaques in Familial Alzheimer's Disease Mice (5xFAD) Brain

Journal article
Authors Ibrahim Kaya
Eva Jennische
J. Dunevall
Stefan Lange
Andrew G Ewing
P. Malmberg
A. T. Baykal
John S. Fletcher
Published in Acs Chemical Neuroscience
Volume 11
Issue 1
Pages 14-24
ISSN 1948-7193
Publication year 2020
Published at Institute of Biomedicine
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Department of Chemistry and Molecular Biology
Pages 14-24
Language en
Links dx.doi.org/10.1021/acschemneuro.9b0...
Keywords Alzheimer's disease, 5xFAD, MALDI imaging mass spectrometry, amyloid, plaques, gangliosides, sialic acid, monosialogangliosides, dentate, gyrus, neurogenesis, imaging mass-spectrometry, apolipoprotein-e, mouse model, beta, gangliosides, lipids, protein, neurogenesis, recognition, metabolism, Biochemistry & Molecular Biology, Pharmacology & Pharmacy, Neurosciences, & Neurology
Subject categories Neurosciences

Abstract

Ganglioside metabolism is significantly altered in Alzheimer's disease (AD), which is a progressive neuro-degenerative disease prominently characterized by one of its pathological hallmarks, amyloid deposits or "senile plaques". While the plaques mainly consist of aggregated variants of amyloid-beta protein (A beta), recent studies have revealed a number of lipid species including gangliosides in amyloid plaques along with A beta peptides. It has been widely suggested that long chain (sphingosine) base (LCBs), C18:1-LCB and C20:1-LCB, containing gangliosides might play different roles in neuronal function in vivo. In order to elucidate region-specific aspects of amyloid-plaque associated C18:1-LCB and C20:1-LCB ganglioside accumulations, high spatial resolution (10 mu m per pixel) matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) of gangliosides in amyloid plaques was performed in hippocampal and adjacent cortical regions of 12 month old 5xFAD mouse coronal brain sections from two different stereotaxic coordinates (bregma points, -2.2 and -2.7 mm). MALDI-IMS uncovered brain-region (2 and 3D) and/or LCB specific accumulations of monosialogangliosides (GMs): GM1, GM2, and GM3 in the hippocampal and cortical amyloid plaques. The results reveal monosialogangliosides to be an important component of amyloid plaques and the accumulation of different gangliosides is region and LCB specific in 12 month old 5xFAD mouse brain. This is discussed in relation to amyloid-associated AD pathogenesis such as lipid related immune changes in amyloid plaques, AD specific ganglioside metabolism, and, notably, AD-associated impaired neurogenesis in the subgranular zone.

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