Proteomics

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LC-MS/MS Isomeric Profiling of N-Glycans derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Im-pairment Patients


ABSTRACT: 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 ob-served 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 con-tributors to the overall pathophysiology of neurodegenerative diseases and be used as a poten-tial 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 de-pleted blood serum samples from MCI patients. For the first time, we profiled the isomeric gly-come 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 HexNAc5,Hex6,Neu5Ac3 and HexNAc6,Hex7,Neu5Ac4 with single AUCs of 0.92 and 0.87 respectively, and combined AUC of 0.96; and the sialylat-ed-fucosylated N-glycans HexNAc4,Hex5,Fuc,Neu5Ac, HexNAc5,Hex6,Fuc,Neu5Ac2 and HexNAc6,Hex7,Fuc,Neu5Ac3 with single AUCs of 0.94, 0.67, and 0.88 respectively, and combined AUC of 0.98. According to ingenuity pathway analysis (IPA) and in line with recent publications the identified N-glycans may play an important role in neuroinflammation. Process that plays a fundamental role in the progression of neurodegenerative diseases.

INSTRUMENT(S): LTQ Orbitrap Velos, TSQ Vantage

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell

DISEASE(S): Mild Cognitive Impairment

SUBMITTER: Cristian Gutierrez Reyes  

LAB HEAD: Yehia Mechref

PROVIDER: PXD036704 | Pride | 2023-03-11

REPOSITORIES: Pride

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LC-MS/MS Isomeric Profiling of <i>N</i>-Glycans Derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Impairment Patients.

Reyes Cristian D Gutierrez CDG   Hakim Md Abdul MA   Atashi Mojgan M   Goli Mona M   Gautam Sakshi S   Wang Junyao J   Bennett Andrew I AI   Zhu Jianhui J   Lubman David M DM   Mechref Yehia Y  

Biomolecules 20221108 11


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  ...[more]

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