Background: Several genome-wide association studies have found that the rs11136000
polymorphism of the C allele (CLU-C) is associated with the risk for developing late-onset Alzheimer’s
disease (LOAD). However, the effects of the CLU-C/C genotype on brain structure, including
gray and white matter, are not adequately understood.
Objectives: We aimed to clarify the gray matter and white matter integrity changes in non-demented
ageing individuals with the AD risk gene of the rs11136000 polymorphism of the C allele (CLU-C)
and the correlation with cognitive performance.
Methods: Voxel-based analysis was used to compare the differences in high-resolution structural T1
and diffusion tensor imaging data between 31 CLU-C/C and 15 non-CLU-C/C carriers in nondemented
Results: Compared to non-CLU-C/C carriers, CLU-C homozygotes showed a reduced gray matter
concentration (GMC) in the left parahippocampal gyrus, right middle frontal and temporal middle
gyri, increased GMC in the left middle frontal and right fusiform gyri and increased gray matter volume
(GMV) in the left middle frontal gyrus (P < 0.001). Decreased fractional anisotropy (FA) in the
sub-gyral white matter of the left external capsule and left anterior cingulate and increased FA in the
sub-gyral white matter of the left temporal lobe were also found in CLU-C/C genotype carriers.
Moreover, the FA value in the left external capsule correlated with several cognitive measures.
Conclusion: Our findings provide further evidence for the CLU risk variant as a candidate gene for
AD and may serve as a pre-clinical neuroimaging phenotype of late-onset AD.