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

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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.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2019-12-12 , DOI: 10.1021/acschemneuro.9b00532
Ibrahim Kaya _{1,

2,

3} , Eva Jennische ₄ , Johan Dunevall ₅ , Stefan Lange ₄ , Andrew G Ewing _{2,

3} , Per Malmberg ₅ , Ahmet Tarik Baykal ₆ , John S Fletcher _{2,

3}

Affiliation

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.

中文翻译：

空间脂质组学揭示家族性阿尔茨海默氏病小鼠（5xFAD）大脑淀粉样斑块中单唾液酸神经节苷脂的区域和长链碱基特异性积聚。

神经节苷脂的代谢在阿尔茨海默氏病（AD）中发生显着改变，该疾病是一种进行性神经退行性疾病，其主要特征是其病理标志之一，淀粉样蛋白沉积或“老年斑”。虽然噬斑主要由淀粉样β蛋白（Aβ）的聚集变体组成，但最近的研究已经揭示了许多脂质种类，包括淀粉样斑块中的神经节苷脂以及Aβ肽。广泛认为，含有神经节苷脂的长链（鞘氨醇）碱基（LCBs），C18：1-LCB和C20：1-LCB可能在体内神经元功能中发挥不同的作用。为了阐明与淀粉样蛋白斑有关的C18：1-LCB和C20：1-LCB神经节苷脂积聚的区域特定方面，在来自两个不同立体定位坐标的12个月大5xFAD小鼠冠状脑切片的海马区和邻近皮质区域中，对淀粉样斑块中神经节苷脂的高空间分辨率（每像素10μm）矩阵辅助激光解吸电离成像质谱（MALDI-IMS）（前reg点-2.2和-2.7毫米）。MALDI-IMS在海马和皮质淀粉样蛋白斑块中发现了单唾液酸神经节苷脂（GM）的脑区域（2和3D）和/或LCB特异性积聚：GM1，GM2和GM3。结果表明，单唾液酸神经节苷脂是淀粉样斑块的重要成分，不同神经节苷脂的积累在12月龄的5xFAD小鼠大脑中是区域和LCB特异性的。讨论了与淀粉样蛋白相关的AD发病机制，例如淀粉样蛋白斑块中与脂质相关的免疫变化，

更新日期：2019-12-13

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