The Role of Changes in the Expression of Inflammation-Associated Genes in Cerebral Small Vessel Disease with Cognitive Impairments

Dobrynina L. A., Makarova A. G., Shabalina A. A., Burmak A. G., Shlapakova P. S., Shamtieva K. V., Tsypushtanova M. M., Trubitsyna V. V., Gnedovskaya E. V.
Neuroscience and Behavioral Physiology, Fri, 5 Apr 2024
To clarify the role of changes in the expression of inflammation-associated genes in cerebral small vessel disease (cSVD). Materials and methods. A total of 44 patients with cSVD (mean age 61.4 ± 9.2 years) and 11 volunteers (mean age 57.3 ± 9.7 years) were investigated. Gene expression was assessed using a custom NanoString nCounter panel of 58 inflammation-associated genes and four reference genes. The gene set was formed on the basis of convergent results from genome-wide association studies (GWAS) in cSVD and Alzheimer’s disease and circulating markers associated with vascular wall and brain damage in cSVD. RNA was isolated from blood leukocytes and analyzed using the nCounter Analysis System, with subsequent analysis in nSolver 4.0. Results were verified by real-time PCR. Results. Patients with cSVD, as compared with controls, had significantly lower levels of expression of BIN1 (log2FC = –1.272; p = 0.039) and VEGFA (log2FC = = –1.441; p = 0.038), which showed predictive ability for cSVD. The threshold value of BIN1 expression was 5.76 U (sensitivity 73%, specificity 75%), and that of VEGFA was 9.27 U (sensitivity 64%, specificity 86%). Decreased expression of VEGFA (p = 0.011), VEGFC (p = 0.017), and CD2AP (p = 0.044) was associated with clinically significant cognitive impairment. A significant direct correlation between Montreal Cognitive Assessment Scale test results and VEGFC expression was found; delayed memory test results correlated with BIN1 and VEGFC expression. Conclusions. The ability to predict the development of cSVD from low BIN1 and VEGFA expression levels and the association between clinically significant cognitive impairments with low VEGFA and VEGFC indicate their importance in the development and progression of the disease. The demonstrated significance of these genes in the pathogenesis of Alzheimer’s disease indicates that similar changes in their expression profile in cSVD may be among the conditions for the comorbidity of the two pathologies.