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Evaluation and Identification of Protein Blood Biomarkers for Alzheimer's Disease: A Systematic Review and Integrative Analysis

Abstract

Junseong Park, JiEun Park, Jungsul Lee and Chulhee Choi

Background: Alzheimer’s disease (AD) accounts for 80% of all dementia, but current treatment cannot provide definite cure. For this reason, researchers seek highly accurate preclinical biomarkers for minimal cognitive impairment. This study aimed to evaluate sporadically reported protein blood biomarkers (BBs) of AD and suggest new protein BB candidates for AD. Methods: A systematic PubMed review was performed on articles published between 1989 and March 2013, and several articles and protein BBs of AD were screened based on eligibility criteria and quality. An integrative analysis was conducted to evaluate reported protein BBs and identify new protein BB candidates. Results: In total, 67 articles were included; 95 protein BBs were evaluated through a meta-scoring system based on five criteria. The highest meta-scored protein BB was Serpin A3 (meta-score: 36) followed by tumor necrosis factor-α(meta-score: 35). An integrative analysis using a protein-protein interaction (PPI) network revealed that 67 proteins are linked via 97 edges. In an extended PPI network, 105 proteins were connected via 240 edges and 63 linker molecules were discovered as new protein BB candidates. Conclusion: This study showed a total of 95 meta-scored protein BBs and identified 63 new biomarker candidates of AD.

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