An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele.
An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele.
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DOI：
10.1186/s13195-023-01239-0
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发表时间：
2023-05-23
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影响因子：
--
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携带载脂蛋白E（ApoE）β 4等位基因与脑淀粉样变性和迟发性阿尔茨海默病的风险增加有关，但apoE糖基化对其发展的影响程度尚不清楚。在先前的初步研究中，我们确定了不同的总和次级亚型特异性脑脊液（CSF）apoE糖基化谱，其中E4亚型具有最低的糖基化百分比（E2 > E3 > E4）。在这项工作中，我们将分析扩展到更大的个体队列（n = 106），利用匹配的血浆和CSF样本与AD生物标志物的临床测量。结果证实了CSF中apoE的亚型特异性糖基化，由继发性CSF apoE糖基化模式引起。CSF apoE糖基化百分比与CSF Aβ42水平呈正相关（r = 0.53，p < 0.0001）。血浆apoE糖基化未观察到这些相关性。CSF总和二级apoE糖基化百分比也与CSF小高密度脂蛋白颗粒（s-HDL-P）浓度相关，我们先前已证明其与CSF Aβ42水平和认知功能指标相关。从CSF中纯化的apoE的去唾液酸化显示小胶质细胞中Aβ42降解减少，E4 > E3，与肝素的结合亲和力增加。这些结果表明apoE糖基化在影响脑Aβ代谢中具有新的重要作用，可作为潜在的治疗靶点。 在线版本包含补充材料，可通过10.1186/s13195-023-01239-0获取。
Carrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer’s disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ42 levels (r = 0.53, p < 0.0001). These correlations were not observed for plasma apoE glycosylation. CSF total and secondary apoE glycosylation percentages also correlated with the concentration of CSF small high-density lipoprotein particles (s-HDL-P), which we have previously shown to be correlated with CSF Aβ42 levels and measures of cognitive function. Desialylation of apoE purified from CSF showed reduced Aβ42 degradation in microglia with E4 > E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment. The online version contains supplementary material available at 10.1186/s13195-023-01239-0.
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影响因子：
7.5
作者：
Itakura Y;Sasaki N;Kami D;Gojo S;Umezawa A;Toyoda M
通讯作者：
Toyoda M
影响因子：
2.9
作者：
Nguyen D;Dhanasekaran P;Nickel M;Nakatani R;Saito H;Phillips MC;Lund-Katz S
通讯作者：
Lund-Katz S
DOI：
10.3233/jad-200203
发表时间：
2020
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Hu Y;Meuret C;Go S;Yassine HN;Nedelkov D
通讯作者：
Nedelkov D
影响因子：
6.1
作者：
Moon, Hee-Jung;Haroutunian, Vahram;Zhao, Liqin
通讯作者：
Zhao, Liqin
影响因子：
15.9
作者：
GREGG, RE;ZECH, LA;BREWER, HB
通讯作者：
BREWER, HB