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

被引:6
作者
Huang, Chu-Chung [1 ,6 ]
Liu, Mu-En [2 ,3 ,4 ]
Kao, Hung-Wen [5 ,8 ]
Chou, Kun-Hsien [6 ]
Yang, Albert C. [2 ,4 ,7 ]
Wang, Ying-Hsiu [2 ]
Chen, Tong-Ru [2 ]
Tsai, Shih-Jen [2 ,4 ]
Lin, Ching-Po [1 ,6 ,8 ]
机构
[1] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan
[2] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan
[3] Natl Yang Ming Univ, Inst Brain Sci, Taipei 112, Taiwan
[4] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan
[5] Natl Def Med Ctr, Triserv Gen Hosp, Dept Radiol, Taipei, Taiwan
[6] Natl Yang Ming Univ, Brain Res Ctr, Taipei 112, Taiwan
[7] Natl Cent Univ, Ctr Dynam Biomarkers & Translat Med, Chungli 32054, Taiwan
[8] Natl Yang Ming Univ, Dept Biomed Imaging & Radiol Sci, Taipei 112, Taiwan
关键词
AMYLOID PRECURSOR PROTEIN; WORKING-MEMORY; ASSOCIATION; GENE; POLYMORPHISMS; ATROPHY;
D O I
10.1038/srep23362
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:8
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