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

Bibliographic Details
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
Source: Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-12 (2018)
Publisher Information: BMC, 2018.
Publication Year: 2018
Collection: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
LCC:Neurology. Diseases of the nervous system
Subject Terms: Anatomical structural covariance, Default mode network, Posterior cingulate cortex, Executive control network, Bcl-2, Polymorphism, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1758-9193
Relation: http://link.springer.com/article/10.1186/s13195-018-0344-4; https://doaj.org/toc/1758-9193
DOI: 10.1186/s13195-018-0344-4
Access URL: https://doaj.org/article/ef0bc3dc55bc4c5fafe047a4e5d03ea6
Accession Number: edsdoj.f0bc3dc55bc4c5fafe047a4e5d03ea6
Database: Directory of Open Access Journals
More Details
ISSN:17589193
DOI:10.1186/s13195-018-0344-4
Published in:Alzheimer’s Research & Therapy
Language:English