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Prognostic Polypeptide Blood Plasma Biomarkers of Alzheimer's Disease Progression

Article type: Research Article

Authors: Yang, Hongqiana | Lyutvinskiy, Yaroslava | Herukka, Sanna-Kaisab | Soininen, Hilkkab | Rutishauser, Dorotheaa | Zubarev, Roman A.a; c; *

Affiliations: [a] Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden | [b] Department of Neurology, School of Medicine, University of Eastern Finland, Kuopio, Finland | [c] SciLifeLab, Stockholm, Sweden

Correspondence: [*] Correspondence to: Roman A. Zubarev, PhD, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Scheelesväg 2, SE 17177 Stockholm, Sweden. Tel.: +46 8524 87594; E-mail: roman.zubarev@ki.se.

Keywords: Biomarkers, human blood plasma, label-free quantification, mass spectrometry

DOI: 10.3233/JAD-132102

Journal: Journal of Alzheimer's Disease, vol. 40, no. 3, pp. 659-666, 2014

Accepted 13 December 2013
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Published: 23 April 2014
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Supplementary Materials:

Supplementary Materials.

Abstract

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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