TY - JOUR
T1 - Spatial Lipidomics Reveals Region and Long Chain Base Specific Accumulations of Monosialogangliosides in Amyloid Plaques in Familial Alzheimer's Disease Mice (5xFAD) Brain
AU - Kaya, Ibrahim
AU - Jennische, Eva
AU - Dunevall, Johan
AU - Lange, Stefan
AU - Ewing, Andrew G.
AU - Malmberg, Per
AU - Baykal, Ahmet Tarik
AU - Fletcher, John S.
N1 - Funding Information:
This study was financially supported by the Swedish Government under the LUA/ALF Agreement, Sahlgrenska University Hospital, the Swedish Research Council (VR), the Knut and Alice Wallenberg Foundation, the USA National Institutes of Health (NIH), European Research Council (ERC), The Scientific and Technological Research Council of Turkey (TUBITAK).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2020/1/2
Y1 - 2020/1/2
N2 - Ganglioside metabolism is significantly altered in Alzheimer's disease (AD), which is a progressive neurodegenerative disease prominently characterized by one of its pathological hallmarks, amyloid deposits or "senile plaques". While the plaques mainly consist of aggregated variants of amyloid-β protein (Aβ), recent studies have revealed a number of lipid species including gangliosides in amyloid plaques along with Aβ 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 μm 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.
AB - Ganglioside metabolism is significantly altered in Alzheimer's disease (AD), which is a progressive neurodegenerative disease prominently characterized by one of its pathological hallmarks, amyloid deposits or "senile plaques". While the plaques mainly consist of aggregated variants of amyloid-β protein (Aβ), recent studies have revealed a number of lipid species including gangliosides in amyloid plaques along with Aβ 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 μm 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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U2 - 10.1021/acschemneuro.9b00532
DO - 10.1021/acschemneuro.9b00532
M3 - Article
C2 - 31774647
AN - SCOPUS:85076755265
VL - 11
SP - 14
EP - 24
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
SN - 1948-7193
IS - 1
ER -