Abstract
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.
Highlights
Levels of cerebrospinal fluid (CSF) Aβ 1-42 were observed in carriers of the Alzheimer disease (AD) risk allele A in Sortilin receptor 1 (SORL1) rs3824968 compared with noncarriers[12], and the decrease in these levels was associated with AD progression[13]
By using a relatively large sample size with a broad age range in combination with an unbiased and whole-brain voxel-based morphometry (VBM) approach, we assessed two hypotheses based on previous studies: (1) independent of the age effect, the variants of SORL1 rs3824968 are associated with the difference of regional grey matter (GM) volume in nondemented adults and (2) SORL1 rs3824968 interacts with age and is associated with regional GM volume alterations across lifespan
We performed VBM analysis to examine the effect of SORL1 rs3824968 on regional GM volume and age-related changes in the brain GM volume of nondemented participants within a wide age range
Summary
Levels of CSF Aβ 1-42 were observed in carriers of the AD risk allele A in SORL1 rs3824968 compared with noncarriers[12], and the decrease in these levels was associated with AD progression[13]. This discrepancy may be owing to ethnic difference, suggesting the existence of population-specific locus It should be noted the reference allele for the SORL1 rs3824968 is the T over all populations. Few studies have systemically investigated the interactions of age, SORL1 effect, and regional grey matter (GM) volume changes in a healthy population. Deducing the risk factors for accelerated brain ageing by evaluating the interaction of SORL1 variants with age and their association with the regional brain volume changes over the adult lifespan would benefit current ageing-related genetic imaging studies. Considering previous findings and the role of SORL1 in the normal ageing process, this study examined regional GM volume changes as an intermediate phenotype in nondemented adults during their lifespan to infer the relationship between the genetic effect of SORL1 rs3824968 and brain ageing. By using a relatively large sample size with a broad age range in combination with an unbiased and whole-brain voxel-based morphometry (VBM) approach, we assessed two hypotheses based on previous studies: (1) independent of the age effect, the variants of SORL1 rs3824968 are associated with the difference of regional GM volume in nondemented adults and (2) SORL1 rs3824968 interacts with age and is associated with regional GM volume alterations across lifespan
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