Spatial Lipidomics Reveals Region and Long Chain Base Specific Accumulations of Monosialogangliosides in Amyloid Plaques in Familial Alzheimer's Disease Mice (5xFAD) Brain
Artikel i vetenskaplig tidskrift, 2020

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.

amyloid plaques

monosialogangliosides

MALDI imaging mass spectrometry

sialic acid

gangliosides

Alzheimer's disease

neurogenesis

dentate gyrus

5xFAD

Författare

Ibrahim Kaya

Göteborgs universitet

Eva Jennische

Göteborgs universitet

Johan Dunevall

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Stefan Lange

Göteborgs universitet

Andrew G. Ewing

Göteborgs universitet

Per Malmberg

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Ahmet Tarik Baykal

Acibadem Mehmet Ali Aydinlar Universitesi

John S. Fletcher

Göteborgs universitet

ACS Chemical Neuroscience

1948-7193 (ISSN)

Vol. 11 1 14-24

Ämneskategorier

Biokemi och molekylärbiologi

Neurovetenskaper

Neurologi

DOI

10.1021/acschemneuro.9b00532

PubMed

31774647

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Senast uppdaterat

2020-04-20