Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer's disease.
Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer's disease.
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DOI：
10.1186/s13195-018-0344-4
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发表时间：
2018-02-08
期刊：
影响因子：
--
通讯作者：
Lien CY
中科院分区：
文献类型：
--
作者：
Chang CC;Chang YT;Huang CW;Tsai SJ;Hsu SW;Huang SH;Lee CC;Chang WN;Lui CC;Lien CY
Alzheimer’s disease (AD) is a complex neurodegenerative disease, and genetic differences may mediate neuronal degeneration. In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain. The Bcl-2 AA genotype has been associated with reduced Bcl-2 levels and lower gray matter volume in healthy populations. We hypothesized that different Bcl-2 genotype groups may modulate large-scale brain networks that determine neurobehavioral test scores. Gray matter structural covariance networks (SCNs) were constructed in 104 patients with AD using T1-weighted magnetic resonance imaging with seed-based correlation analysis. The patients were stratified into two genotype groups on the basis of Bcl-2 expression (G carriers, n = 76; A homozygotes, n = 28). Four SCNs characteristic of AD were constructed from seeds in the default mode network, salience network, and executive control network, and cognitive test scores served as the major outcome factor. For the G carriers, influences of the SCNs were observed mostly in the default mode network, of which the peak clusters anchored by the posterior cingulate cortex seed determined the cognitive test scores. In contrast, genetic influences in the A homozygotes were found mainly in the executive control network, and both the dorsolateral prefrontal cortex seed and the interconnected peak clusters were correlated with the clinical scores. Despite a small number of cases, the A homozygotes showed greater covariance strength than the G carriers among all four SCNs. Our results suggest that the Bcl-2 rs956572 polymorphism is associated with different strengths of structural covariance in AD that determine clinical outcomes. The greater covariance strength in the four SCNs shown in the A homozygotes suggests that different Bcl-2 polymorphisms play different modulatory roles. The online version of this article (10.1186/s13195-018-0344-4) contains supplementary material, which is available to authorized users.
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影响因子：
34.7
作者：
Alexander-Bloch, Aaron;Giedd, Jay N.;Bullmore, Edward T.
通讯作者：
Bullmore, Edward T.
DOI：
10.1017/s1355617709991184
发表时间：
2010-03
影响因子：
2.6
作者：
Chang, Chiung Chih;Kramer, Joel H.;Lin, Ker Neng;Chang, Wen Neng;Wang, Ya-Ling;Huang, Chi-Wei;Lin, Yu Ting;Chen, Ching;Wang, Pei Ning
通讯作者：
Wang, Pei Ning
影响因子：
--
作者：
Lin PH;Tsai SJ;Huang CW;Mu-En L;Hsu SW;Lee CC;Chen NC;Chang YT;Lan MY;Chang CC
通讯作者：
Chang CC
DOI：
10.1098/rstb.2005.1634
发表时间：
2005-05-29
影响因子：
6.3
作者：
Beckmann, CF;DeLuca, M;Smith, SM
通讯作者：
Smith, SM
影响因子：
6.7
作者：
Huang, Chi-Wei;Tsai, Meng-Han;Chang, Chiung-Chih
通讯作者：
Chang, Chiung-Chih