Modulation effect of the SORL1 gene on functional connectivity density in healthy young adults

The sortilin-related receptor 1 (SORL1) gene has been associated with late-onset Alzheimer's disease (LOAD) and structural impairments in several ethnic populations. However, how this gene affects brain function properties remains unclear. We investigated associations of SORL1 rs2070045 with functional connectivity density (FCD) in healthy young adults. This single-nucleotide polymorphism was selected because it is the SORL1 variant that has been frequently associated with LOAD in several populations, including the Chinese Han population. A total of 275 healthy young Chinese Han subjects with successful genotyping and MRI examinations were included. The effect of SORL1 rs2070045 was explored using a voxel-wise FCD analysis. A significant effect of SORL1 rs2070045 on the FCD was found in the right inferior temporal gyrus. The risk G allele carriers of the rs2070045 exhibited a lower FCD than the protective TT carriers. This effect was independent of the status of apolipoprotein E. This study provides the first evidence that the SORL1 gene is associated with brain FCD differences in healthy young adults. In the genetic risk subjects, connectivity impairment already starts during young adulthood, which may predispose the risk allele carriers to be susceptible to LOAD after several decades.