title: Prognostic polypeptide blood plasma biomarkers of Alzheimer's disease progression.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Hongqian
authors: H
authors: Yang
authors: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Yaroslav
authors: Y
authors: Lyutvinskiy
authors: Department of Neurology, School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Sanna-Kaisa
authors: SK
authors: Herukka
authors: Department of Neurology, School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Hilkka
authors: H
authors: Soininen
authors: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Dorothea
authors: D
authors: Rutishauser
authors: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden SciLifeLab, Stockholm, Sweden.
authors: Roman A
authors: RA
authors: Zubarev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000097:blood*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010455:Peptides / Q000032:analysis / Q000097:blood; D011506:Proteins / Q000032:analysis; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D010455:Peptides; D011506:Proteins
keywords: Biomarkers; human blood plasma; label-free quantification; mass spectrometry