Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 40, Issue 3, Pages 659-666Publisher
IOS PRESS
DOI: 10.3233/JAD-132102
Keywords
Biomarkers; human blood plasma; label-free quantification; mass spectrometry
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Funding
- EU
- Knut and Alice Wallenberg Foundation
- VINNOVA Foundation
- Alzheimerfonden
- Swedish Research council
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Background: Patients with mild cognitive impairment (MCI) have varying risks of progression to Alzheimer's disease (AD). Objective: To test the utility of the relative abundances of blood plasma polypeptides for predicting the risk of AD progression. Methods: 119 blood plasma samples of patients with MCI with different outcomes (stable MCI and progressive MCI) were analyzed by untargeted, label-free shotgun proteomics. Predictive biomarkers of progressive MCI were selected by multivariate analysis, followed by cross-validation of the predictive model. Results: The best model demonstrated the accuracy of ca. 79% in predicting progressive MCI. Sex differences of the predictive biomarkers were also assessed. We have identified some sex-specific protein biomarkers, e.g., alpha-2-macrogloblin (A2M), which strongly correlates with female AD progression but not with males. Conclusion: Significant sex bias in AD-specific biomarkers underscores the necessity of selecting sex-balanced cohort in AD biomarker studies, or using sex-specific models. Blood protein biomarkers are found to be promising for predicting AD progression in clinical settings.
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