Abstract
BackgroundInflammatory processes play a pivotal role in the degenerative process of Alzheimer’s disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer’s disease.MethodsWe enrolled a total of 135 patients with Alzheimer’s disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations.ResultsThere were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores.ConclusionsInterleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.
Highlights
Inflammatory processes play a pivotal role in the degenerative process of Alzheimer’s disease
Patterns of Structural covariance networks (SCNs) and genetic variants A direct comparison between the gray matter (GM) volume of Ccarriers or T homozygotes using voxel-based morphometry [54] showed no significant volumetric differences
According to the genotype classification (C-carriers and TT-carriers) and four seeds (Fig. 1a), there were no significant differences in the GM volumes of each seed (Fig. 1b)
Summary
Inflammatory processes play a pivotal role in the degenerative process of Alzheimer’s disease. We investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer’s disease. The neuropathology of Alzheimer’s disease (AD) involves a profound innate immune response and production of inflammatory cytokines [1]. Many inflammatory mediators have been identified in the brains of patients with AD. Variations in inflammatory-related genes have been extensively investigated [5,6,7,8], and the expression of interleukin-1 (IL-1) beta has been shown to have clinical relevance. In an Alzheimer’s mouse model, IL-1 betarelated inflammatory responses surprisingly reduced amyloid beta deposition [10] but paradoxically enhanced tau pathology [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
