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. 2024 Jul 25;25(15):8113.
doi: 10.3390/ijms25158113.

The Role of Changes in the Expression of Inflammation-Associated Genes in the Variants of Cerebral Small Vessel Disease

Larisa A Dobrynina  1 , Angelina G Makarova  1 , Alla A Shabalina  1 , Anastasiia G Burmak  1 , Polina S Shlapakova  1 , Kamila V Shamtieva  1 , Maria M Tsypushtanova  1 , Elena I Kremneva  1 , Maryam R Zabitova  1 , Alexey S Filatov  1 , Elena V Gnedovskaya  1
Affiliations

The Role of Changes in the Expression of Inflammation-Associated Genes in the Variants of Cerebral Small Vessel Disease

Larisa A Dobrynina et al. Int J Mol Sci. .

Abstract

Age-dependent cerebral small vessel disease (CSVD) is a common disease with a high social burden characterized by heterogeneity of forms and frequent comorbidity with Alzheimer's disease (AD). Previously, we identified two MRI types of CSVD with specific clinical presentation and, probably, different mechanisms. The present study included 34 patients with CSVD and white matter hyperintensity (WMH) of stage Fazekas (F) 3 (mean age 61.7 ± 8.9) and 11 volunteers (mean age 57.3 ± 9.7). Total RNA was isolated from peripheral blood leukocytes. The expression of 58 protein-coding genes associated with CSVD and/or AD and 4 reference genes were assessed as part of the original panel for the NanoString nCounter analyzer. Testing results were validated by real-time PCR. There was a significant decrease in the expression levels of the ACOX1, CD33, CD2AP, TNFR1, and VEGFC genes in MRI type 2 relative to the control group as well as a decrease in the expression level of the CD33 gene in MRI type 2 compared to MRI type 1. Processes associated with inflammatory pathways with decreased expression of the identified genes are important in the development of MRI type 2 of CSVD. Given the direct connection of the established genes with AD, the importance of this form of CSVD in comorbidity with AD has been assumed.

Keywords: Alzheimer’s disease; MRI types; cerebral small vessel disease; differential gene expression; direct digital RNA detection method; inflammation-associated genes; white matter hyperintensity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Comparison of gene expression between CSVD and controls.
Figure 2
Figure 2
Comparison of gene expression between MRI types and controls.
Figure 3
Figure 3
A heat map of the normalized gene expression level of MRI type 2 and control group patients. A is the control group; B is the main group. An increase in the intensity of the blue scale reflects a decrease in the level of expression, while the yellow scale reflects an increase in the level of expression.
Figure 4
Figure 4
ROC curve of predictive value for clinically significant CI in MRI type 2 CSVD with reduced expression of ACOX1 and VEGFA.
Figure 5
Figure 5
A dendrogram of the hierarchical classification of 187 patients with CSVD with the allocation of two large clusters—MRI type 1 and MRI type 2.
See this image and copyright information in PMC

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