The Impact of UNC5C Genetic Variations on Neuroimaging in Alzheimer's Disease

UNC5C, which is a transmembrane receptor for netrin-1 to trigger the apoptosis, has been confirmed as a new risk factor for Alzheimer's disease (AD) recently. However, there is lack of the evidence on the brain structure associated with the polymorphisms of UNC5C in AD. The objective of this study is to investigate the influence of UNC5C loci on the neuroimaging of strategic regions of AD. In 812 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we explored the genotypes of UNC5C loci in the volumes of the hippocampus, parahippocampal gyrus, posterior cingulate gyrus, middle temporal and precuneus, and the thickness of the entorhinal cortex which are measured by magnetic resonance imaging (MRI). We also investigated the atrophy rate of above structures influenced by UNC5C loci using the longitudinal data. UNC5C loci were associated with the volume of right middle temporal (rs34585936 P-c = 0.0031). Meanwhile, the polymorphisms of UNC5C loci could alter the atrophy rate of strategic regions especially the left hippocampus (rs72672784 P-c = 0.0090; rs13120458 P-c = 0.0434; rs34875919 P-c = 0.0434) and right precuneus (rs72672784 P-c = 0.0068; rs2001246 P-c = 0.0055; rs74690179 P-c = 0.0055). UNC5C genotypes were significantly associated with the volume of the middle temporal on MRI; meanwhile, UNC5C loci could alter the atrophy of strategic regions of AD such as the hippocampus and precuneus. And the above effects of polymorphisms of UNC5C were more obvious in the population with the impaired cognition than those with the normal cognition.