Brain-wide structural connectivity alterations under the control of Alzheimer risk genes

Abstract

Alzheimer's disease is the most common form of brain dementia characterised by gradual loss of memory. Large-scale genome-wide association studies (GWASs) have identified some AD risk genes, but their relationship with the brain-wide network breakdown in AD remains unknown. Using the genotype and diffusion tensor imaging (DTI) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we performed a targeted genetic association analysis of three types of link measures, including fibre anisotropy, fibre length and density. For fair comparison, all link measures were normalised with zero mean and unit standard deviation. We focused on 34 AD risk SNPs identified in previous GWAS studies. After Bonferroni correction, rs10498633 in SLC24A4 was found to be significantly associated with anisotropy, total number and length of fibres. rs429358 in top AD risk gene APOE showed nominal significance of association with the density of fibres between subcortical and cerebellum regions.