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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2018

Open Access 01-12-2018 | Research

Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer’s disease

Authors: Chiung-Chih Chang, Ya-Ting Chang, Chi-Wei Huang, Shih-Jen Tsai, Shih-Wei Hsu, Shu-Hua Huang, Chen-Chang Lee, Wen-Neng Chang, Chun-Chung Lui, Chia-Yi Lien

Published in: Alzheimer's Research & Therapy | Issue 1/2018

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer’s disease
Authors
Chiung-Chih Chang
Ya-Ting Chang
Chi-Wei Huang
Shih-Jen Tsai
Shih-Wei Hsu
Shu-Hua Huang
Chen-Chang Lee
Wen-Neng Chang
Chun-Chung Lui
Chia-Yi Lien
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-018-0344-4

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