Combination of Serum and Plasma Biomarkers Could Improve Prediction Performance for Alzheimer’s Disease

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Alzheimer’s disease (AD) can be predicted either by serum or plasma biomarkers, and a combination may increase predictive power, but due to the high complexity of machine learning, it may also incur overfitting problems. In this paper, we investigated whether combining serum and plasma biomarkers with feature selection could improve prediction performance for AD. 150 D patients and 150 normal controls (NCs) were enrolled for a serum test, and 100 patients and 100 NCs were enrolled for the plasma test. Among these, 79 ADs and 65 NCs had serum and plasma samples in common. A 10 times repeated 5-fold cross-validation model and a feature selection method were used to overcome the overfitting problem when serum and plasma biomarkers were combined. First, we tested to see if simply adding serum and plasma biomarkers improved prediction performance but also caused overfitting. Then we employed a feature selection algorithm we developed to overcome the overfitting problem. Lastly, we tested the prediction performance in a 10 times repeated 5-fold cross validation model for training and testing sets. We found that the combined biomarkers improved AD prediction but also caused overfitting. A further feature selection based on the combination of serum and plasma biomarkers solved the problem and produced an even higher prediction performance than either serum or plasma biomarkers on their own. The combined feature-selected serum–plasma biomarkers may have critical implications for understanding the pathophysiology of AD and for developing preventative treatments.

Original languageEnglish
Article number1738
Issue number10
StatePublished - Oct 2022


  • Alzheimer’s disease
  • blood biomarkers
  • feature selection
  • machine learning
  • support vector machine


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