Integrative analyses of neuroimaging, clinical, and multi-omics data identified meaningful Alzheimer’s disease progression subtypes

Abstract

Alzheimer’s Disease (AD) is a common neurodegenerative disorder with diverse clinical manifestations. To better understand differences between diverse manifestations, we investigate from the difference in MRI ROI volumes among subtypes to their related different gene pathways. In this study, we identify three subtypes of AD development with fast, moderate, and slow progression rates from the MRI ROI volume biomarkers in the ADNI cohort. We further find differentially expressed proteins in CSF fluids among these AD patients and related significantly different genetic pathways. A total of 159 patients’ data are included for analysis. We identify three distinct subtypes from the hierarchical clustering on MRI ROI volume biomarkers. Subtype 1, characterized as fast progression, consists of 34 patients (21.9%). Subtype 2, as moderate progression, comprises 77 patients (49.6%). Subtype 3, as slow progression, consists of 44 patients (28.3%). These subtypes show significantly differences in cognitive test scores and corresponding genetic pathways.