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Sortilin receptor 1 ( SORL1 ) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a  SORL1  single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of  SORL1  rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between  SORL1  rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21–92 years). Through voxel-based morphometry, we found that participants carrying  SORL1  allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and  SORL1  suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that  SORL1  rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan.

Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Age-Related Interaction in Adult Lifespan