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Differential expression of N-glycopeptides derived from serum glycoproteins in mild cognitive impairment (MCI)
Cristian D Gutierrez Reyes1, Mojgan Atashi1, Mojibola Fowowe1
1Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, USA.
Abstract:
Mild cognitive impairment (MCI) is an early stage of memory loss that affects cognitive abilities with the aging of individuals, such as language or visual/spatial comprehension. MCI is considered a prodromal phase of more complicated neurodegenerative diseases such as Alzheimer's. Therefore, accurate diagnosis and better understanding of the disease prognosis will facilitate prevention of neurodegeneration. However, the existing diagnostic methods fail to provide precise and well-timed diagnoses, and the pathophysiology of MCI is not fully understood. Alterations of the serum N-glycoproteome expression could represent an essential contributor to the overall pathophysiology of neurodegenerative diseases and be used as a potential marker to assess MCI diagnosis using less invasive procedures. In this approach, we identified N-glycopeptides with different expressions between healthy and MCI patients from serum glycoproteins. Seven of the N-glycopeptides showed outstanding AUC values, among them the antithrombin-III Asn224 + 4-5-0-2 with an AUC value of 1.00 and a p value of 0.0004. According to proteomics and ingenuity pathway analysis (IPA), our data is in line with recent publications, and the glycoproteins carrying the identified N-sites play an important role in neurodegeneration.
Insights
Researchers identified specific N-glycopeptides in blood serum that can help diagnose mild cognitive impairment (MCI), an early sign of neurodegenerative diseases like Alzheimer's. This discovery offers a less invasive diagnostic approach for memory loss conditions.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Mild cognitive impairment (MCI) is an early stage of cognitive decline associated with aging.
- MCI is a precursor to neurodegenerative diseases, including Alzheimer's disease.
- Current diagnostic methods for MCI lack precision and timeliness, and its pathophysiology is not fully understood.
Purpose of the Study:
- To investigate serum N-glycoproteome alterations as potential biomarkers for MCI diagnosis.
- To identify specific N-glycopeptides that differentiate between healthy individuals and MCI patients.
- To explore the role of N-glycoproteins in the pathophysiology of neurodegeneration.
Main Methods:
- Serum glycoproteins were analyzed to identify differentially expressed N-glycopeptides between healthy and MCI cohorts.
- Proteomics and Ingenuity Pathway Analysis (IPA) were employed for data interpretation.
- Statistical analysis, including AUC values, was used to assess the diagnostic potential of identified markers.
Main Results:
- Seven N-glycopeptides demonstrated significant differences in expression between healthy and MCI groups.
- The antithrombin-III Asn224 + 4-5-0-2 N-glycopeptide showed a perfect AUC of 1.00 (p=0.0004).
- Proteomics and IPA results align with existing literature, highlighting the role of identified glycoproteins in neurodegeneration.
Conclusions:
- Serum N-glycoproteome profiling can serve as a valuable, less invasive tool for MCI diagnosis.
- Specific N-glycopeptides, such as antithrombin-III Asn224 + 4-5-0-2, show high potential as diagnostic biomarkers for MCI.
- These findings contribute to understanding the pathophysiology of MCI and neurodegeneration.
