What PLS can still do for Imaging Genetics in Alzheimer's disease

Abstract

In this work we exploited Partial Least Squares (PLS) model for analyzing the genetic underpinning of grey matter atrophy in Alzheimer's Disease (AD). To this end, 42 features derived from T1-weighted Magnetic Resonance Imaging, including cortical thicknesses and subcortical volumes were considered to describe the imaging phenotype, while the genotype information consisted of 14 recently proposed AD related Polygenic Risk Scores (PRS), calculated by including Single Nucleotide Polymorphism passing different significance thresholds. The PLS model was applied on a large study cohort obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database including both healthy individuals and AD patients, and validated on an independent ADNI Mild Cognitive Impairment (MCI) cohort, including Early (EMCI) and Late MCI (LMCI). The experimental results confirm the existence of a joint dynamics between brain atrophy and genotype data in AD, while providing important generalization results when tested on a clinically heterogeneous cohort. In particular, less AD specific PRS scores were negatively correlated with cortical thicknesses, while highly AD specific PRSs showed a peculiar correlation pattern among specific subcortical volumes and cortical thicknesses. While the first outcome is in line with the well known neurodegeneration process in AD, the second could be revealing of different AD subtypes.