Salminen Lauren E, Schofield Peter R, Pierce Kerrie D, Zhao Yi, Luo Xi, Wang Youdan, Laidlaw David H, Cabeen Ryan P, Conturo Thomas E, Tate David F, Akbudak Erbil, Lane Elizabeth M, Heaps Jodi M, Bolzenius Jacob D, Baker Laurie M, Cagle Lee M, Paul Robert H
University of Missouri-St. Louis, Department of Psychological Sciences, 1 University Blvd., Stadler Hall 442A, St. Louis, MO 63121, USA.
Neuroscience Research Australia, Barker Street Randwick, Sydney, NSW 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Behav Brain Res. 2016 Jan 1;296:85-93. doi: 10.1016/j.bbr.2015.08.028. Epub 2015 Aug 28.
The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n=27, ThrThr n=27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden.
常见的血管紧张素原（AGT）M268T多态性（rs699；历史上称为M235T）已被确定为脑血管疾病的一个重要风险因素，但尚不清楚携带苏氨酸氨基酸变体的健康老年人在特定纤维束中发生白质损伤的风险是否更高。此外，苏氨酸变体对认知功能的影响仍然未知。本研究利用扩散张量成像（DTI）的多个指标和神经心理学评估，来检查M268T纯合基因型个体（甲硫氨酸/甲硫氨酸，n = 27；苏氨酸/苏氨酸，n = 27）之间特定白质束的完整性和认知情况。还检查了两组之间皮质下高信号（SH）体积的差异。结果表明，与携带甲硫氨酸变体的个体相比，苏氨酸变体与上纵束（SLF）和扣带束的扣带回段（扣带CG）的完整性显著降低有关，并且在注意力/处理速度和语言测试中的认知表现较差。尽管存在这些关联，但这些纤维束的完整性并未显著介导认知与基因状态之间的关系，并且两组之间的SH没有显著差异。我们的研究结果共同表明，M268T的苏氨酸变体是健康老年人特定白质束和认知领域异常的一个重要风险因素，与SH负担无关。
