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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
Univ Gothenburg, Sahlgrenska Acad, Dept Psychiat & Neurochem, S-43180 Molndal, Sweden;Univ Gothenburg, Dept Chem & Mol Biol, S-40530 Gothenburg, Sweden;Univ Gothenburg, Gothenburg Imaging Mass Spectrometry Go IMS Platf, Gothenburg, Sweden;Chalmers Univ Technol, Gothenburg, Sweden.ORCID iD: 0000-0003-3345-5602
Univ Gothenburg, Inst Biomed, S-40530 Gothenburg, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Chalmers Univ Technol, Dept Chem & Chem Engn, S-41296 Gothenburg, Sweden.ORCID iD: 0000-0001-9188-9893
Univ Gothenburg, Inst Biomed, S-40530 Gothenburg, Sweden.
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2020 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 11, no 1, p. 14-24Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2020. Vol. 11, no 1, p. 14-24
Keywords [en]
Alzheimer's disease, 5xFAD, MALDI imaging mass spectrometry, amyloid plaques, gangliosides, sialic acid, monosialogangliosides, dentate gyrus, neurogenesis
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-403496DOI: 10.1021/acschemneuro.9b00532ISI: 000506085400003PubMedID: 31774647OAI: oai:DiVA.org:uu-403496DiVA, id: diva2:1389454
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationEU, European Research CouncilAvailable from: 2020-01-30 Created: 2020-01-30 Last updated: 2020-01-30Bibliographically approved

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