Dataset Information

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

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.

SUBMITTER: Huang CC

PROVIDER: S-EPMC4800313 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Huang Chu-Chung CC Liu Mu-En ME Kao Hung-Wen HW Chou Kun-Hsien KH Yang Albert C AC Wang Ying-Hsiu YH Chen Tong-Ru TR Tsai Shih-Jen SJ Lin Ching-Po CP

Scientific reports 20160321

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 rs382496 ...[more]

PMID: 26996954

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Project description:BackgroundDespite decades of research, there is continued uncertainty regarding whether autism is associated with a specific profile of gray matter (GM) structure. This inconsistency may stem from the widespread use of voxel-based morphometry (VBM) methods that combine indices of GM density and GM volume. If GM density or volume, but not both, prove different in autism, the traditional VBM approach of combining the two indices may obscure the difference. The present study measures GM density and volume separately to examine whether autism is associated with alterations in GM volume, density, or both.MethodsDifferences in MRI-based GM density and volume were examined in 6-25 year-olds with a diagnosis of autism spectrum disorder (n = 213, 80.8% male, IQ 47-154) and a typically developing (TD) sample (n = 190, 71.6% male, IQ 67-155). High-resolution T1-weighted anatomical images were collected on a single MRI scanner. Regional density and volume were estimated via whole-brain parcellation comprised of 1625 parcels. Parcel-wise analyses were conducted using generalized additive models while controlling the false discovery rate (FDR, q < 0.05). Volume differences in the 68-region Desikan-Killiany atlas derived from Freesurfer were also examined, to establish the generalizability of findings across methods.ResultsNo density differences were observed between the autistic and TD groups, either in individual parcels or whole brain mean density. Increased volume was observed in autism compared to the TD group when controlling for Age, Sex, and IQ, both at the level of the whole brain (total volume) and in 45 parcels (2.8% of total parcels). Parcels with greater volume included inferior, middle, and superior temporal gyrus, inferior and superior frontal gyrus, precuneus, and fusiform gyrus. Converging evidence from a standard Freesurfer pipeline also identified greater volume in a number of overlapping regions.LimitationsThe method for determining "density" is not a direct measure of neuronal density, and this study cannot reveal underlying cellular differences. While this study represents possibly the largest single-site sample of its kind, it is underpowered to detect very small differences.ConclusionsThese results provide compelling evidence that autism is associated with regional GM volumetric differences, which are more prominent than density differences. This underscores the importance of examining volume and density separately, and suggests that direct measures of volume (e.g. region-of-interest or tensor-based morphometry approaches) may be more sensitive to autism-relevant differences in neuroanatomy than concentration/density-based approaches.

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Dataset Information

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

Publications

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

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