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MOLECULAR SUBTYPING OF MILD COGNITIVE IMPAIRMENT BASED ON GENETIC POLYMORPHISM AND GENE EXPRESSION

H.-T. Li, S.-X. Yuan, J.-S. Wu, X.-Z. Zhang, Y. Liu, X. Sun, For the Alzheimer’s Disease Neuroimaging Initiative

Background: Alzheimer’s Disease (AD) is a neurodegenerative brain disease in the elderly. Recent studies have revealed the heterogeneous nature of AD. Mild Cognitive Impairment (MCI) is the prodromal stage of AD. Objectives: In this study, we identified subtypes of MCI based on genetic polymorphism and gene expression. Methods: We utilized the two types of omics data, namely genetic polymorphism and gene expression profiling, derived from 125 MCI patients’ peripheral blood samples from the ADNI-1 dataset. Similarity network fusion (SNF) algorithm was implemented to cluster MCI patient subtypes. And 185 MCI patients in ADNI-2 were utilized to evaluate the effectiveness of this method. Two MCI subtypes were identified by implementing the SNF algorithm. Results: We used Kaplan-Meier analysis and log-rank testing for the conversion from MCI to AD between two subtypes, and p-value is 4.58×10-3. In addition, we compared patients among two MCI subtypes by the following factors: the changes in Alzheimer’s Disease cognitive scales and MRI image; significantly enriched pathways based on differentially expressed genes. This study proved that MCI is a heterogeneous disease by concluding that AD development in two MCI subtypes is significantly different. Conclusions: MCI patients with different molecular characteristics have different risks converting to AD. In addition to evaluating statistics, genetic polymorphism and gene expression profiling from MCI patients’ peripheral blood are non-invasiveness and cost-effectiveness markers to identify MCI subtypes for clinical application.

CITATION:
H.-T. Li ; S.-X. Yuan ; J.-S. Wu ; X.-Z. Zhang ; Y. Liu ; X. Sun ; and For the Alzheimer’s Disease Neuroimaging Initiative (2020): Molecular Subtyping of Mild Cognitive Impairment based on Genetic Polymorphism and Gene Expression. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2020.65

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