LC-MS/MS Isomeric Profiling of N-Glycans Derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Impairment Patients.
LC-MS/MS Isomeric Profiling of N-Glycans Derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Impairment Patients.
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DOI：
10.3390/biom12111657
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发表时间：
2022-11-08
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
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轻度认知障碍（MCI）是记忆丧失的早期阶段，影响认知能力，如语言或虚拟/空间理解。这种认知能力的下降主要是随着个体的衰老而观察到的。最近，MCI被认为是阿尔茨海默病（AD）的前驱期，转化率为10-15%。然而，现有的诊断方法未能提供精确和及时的诊断，MCI的病理生理学尚未完全了解。血清N-聚糖表达的改变可能代表神经退行性疾病的整体病理生理学的重要贡献者，并可用作使用非侵入性程序评估MCI诊断的潜在标志物。在此，我们采用LC-MS/MS糖组学方法来确定和表征MCI患者的耗尽血清样品中的潜在N-聚糖标志物。我们首次使用LC-MS/MS分析策略分析了从对照和MCI患者的血清样品中提取的低丰度血清糖蛋白的异构体糖组。此外，鉴定数据的MRM验证显示了五种异构N-聚糖具有区分健康和MCI患者的能力：唾液酸化N-聚糖GlcNAc 5、Hex 6、Neu 5Ac 3和GlcNAc 6、Hex 7、Neu 5Ac 4，其单个AUC分别为0.92和0.87，组合AUC为0.96;和唾液酸化-岩藻糖基化N-聚糖GlcNAc 4、Hex 5、Fuc、Neu 5Ac、GlcNAc 5、Hex 6、Fuc、Neu 5Ac 2和GlcNAc 6、Hex 7、Fuc、Neu 5Ac 3，单个AUC分别为0.94、0.67和0.88，组合AUC为0.98。根据独创性途径分析（IPA）和最近的出版物，确定的N-聚糖可能在神经炎症中发挥重要作用。这是一个在神经炎症中起基础作用的过程，神经炎症是神经退行性疾病进展中的一个重要过程。
Mild cognitive impairment (MCI) is an early stage of memory loss that affects cognitive abilities, such as language or virtual/spatial comprehension. This cognitive decline is mostly observed with the aging of individuals. Recently, MCI has been considered as a prodromal phase of Alzheimer’s disease (AD), with a 10–15% conversion rate. However, the existing diagnostic methods fail to provide precise and well-timed diagnoses, and the pathophysiology of MCI is not fully understood. Alterations of serum N-glycan expression could represent essential contributors to the overall pathophysiology of neurodegenerative diseases and be used as a potential marker to assess MCI diagnosis using non-invasive procedures. Herein, we undertook an LC-MS/MS glycomics approach to determine and characterize potential N-glycan markers in depleted blood serum samples from MCI patients. For the first time, we profiled the isomeric glycome of the low abundant serum glycoproteins extracted from serum samples of control and MCI patients using an LC-MS/MS analytical strategy. Additionally, the MRM validation of the identified data showed five isomeric N-glycans with the ability to discriminate between healthy and MCI patients: the sialylated N-glycans GlcNAc5,Hex6,Neu5Ac3 and GlcNAc6,Hex7,Neu5Ac4 with single AUCs of 0.92 and 0.87, respectively, and a combined AUC of 0.96; and the sialylated-fucosylated N-glycans GlcNAc4,Hex5,Fuc, Neu5Ac, GlcNAc5,Hex6,Fuc, Neu5Ac2, and GlcNAc6,Hex7,Fuc, Neu5Ac3 with single AUCs of 0.94, 0.67, and 0.88, respectively, and a combined AUC of 0.98. According to the ingenuity pathway analysis (IPA) and in line with recent publications, the identified N-glycans may play an important role in neuroinflammation. It is a process that plays a fundamental role in neuroinflammation, an important process in the progression of neurodegenerative diseases.
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影响因子：
5.5
作者：
Helm J;Hirtler L;Altmann F
通讯作者：
Altmann F
影响因子：
4.3
作者：
Akasaka-Manya, Keiko;Manya, Hiroshi;Endo, Tamao
通讯作者：
Endo, Tamao
影响因子：
16.2
作者：
Bermingham, Mairead L.;Colombo, Marco;Colhoun, Helen M.
通讯作者：
Colhoun, Helen M.
影响因子：
2
作者：
Klein, Andre;Carre, Yoann;Morelle, Willy
通讯作者：
Morelle, Willy
DOI：
10.1016/j.jalz.2011.03.008
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Albert MS;DeKosky ST;Dickson D;Dubois B;Feldman HH;Fox NC;Gamst A;Holtzman DM;Jagust WJ;Petersen RC;Snyder PJ;Carrillo MC;Thies B;Phelps CH
通讯作者：
Phelps CH