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Dobrynina L.A.

Research Center of Neurology

Makarova A.G.

Research Center of Neurology

Shabalina A.A.

Research Center of Neurology

Burmak A.G.

Research Center of Neurology

Shlapakova P.S.

Research Center of Neurology

Shamtieva K.V.

Research Center of Neurology

Tsypushtanova M.M.

Research Center of Neurology

Trubitsyna V.V.

Research Center of Neurology

Gnedovskaya E.V.

Research Center of Neurology

A role of altered inflammation-related gene expression in cerebral small vessel disease with cognitive impairment

Authors:

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.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(9): 58‑68

DOI: 10.17116/jnevro202312309158

Read: 2512 times

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Table of contents

A ROLE OF ALTERED INFLAMMATION-RELATED GENE EXPRESSION IN CEREBRAL SMALL VESSEL DISEASE WITH COGNITIVE IMPAIRMENT
A ROLE OF ALTERED INFLAMMATION-RELATED GENE EXPRESSION IN CEREBRAL SMALL VESSEL DISEASE WITH COGNITIVE IMPAIRMENT

To cite this article:

Dobrynina LA, Makarova AG, Shabalina AA, et al. . A role of altered inflammation-related gene expression in cerebral small vessel disease with cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(9):58‑68. (In Russ.)
https://doi.org/10.17116/jnevro202312309158

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)
 
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Abstract:

OBJECTIVE

To identify the role of changes in the expression of inflammation-related genes in cerebral microangiopathy/cerebral small vessel disease (cSVD).

MATERIAL AND METHODS

Forty-four cSVD patients (mean age 61.4±9.2) and 11 controls (mean age 57.3±9.7) were studied. Gene expression was assessed on an individual NanoString nCounter panel of 58 inflammation-related genes and 4 reference genes. A set of genes was generated based on converging results of complete genome-wide association studies (GWAS) in cSVD and Alzheimer’s disease (AD) and circulating markers associated with vascular wall and Brain lesions in cSVD. RNA was isolated from blood leukocytes and analyzed with the nCounter Analysis System, followed by analysis in nSolver 4.0. Results were verified by real-time PCR.

RESULTS

CSVD patients had a significant decrease in BIN1 (log2FC=–1.272; p=0.039) and VEGFA (log2FC=–1.441; p=0.038) expression compared to controls, which showed predictive ability for cSVD. The cut-off for BIN1 expression was 5.76 a.u. (sensitivity 73%; specificity 75%) and the cut-off for VEGFA expression was 9.27 a.u. (sensitivity 64%; specificity 86%). Reduced expression of VEGFA (p=0.011), VEGFC (p=0.017), CD2AP (p=0.044) was associated with cognitive impairment (CI). There was a significant direct correlation between VEGFC expression and the scores on the Montreal Cognitive Assessment test and between BIN1 and VEGFC expression and delayed memory.

CONCLUSION

The possible prediction of cSVD by reduced expression levels of BIN1, VEGFA and the association of clinically significant CI with reduced VEGFA and VEGFC expression indicate their importance in the development and progression of the disease. The established importance of these genes in the pathogenesis of AD suggests that similar changes in their expression profile in cSVD may be one of the conditions for the comorbidity of the two pathologies.

Keywords:

cerebral microangiopathy
small vessel disease
Alzheimer’s disease
gene expression
inflammation
genome-wide association study

Authors:

Dobrynina L.A.

Research Center of Neurology

Makarova A.G.

Research Center of Neurology

Shabalina A.A.

Research Center of Neurology

Burmak A.G.

Research Center of Neurology

Shlapakova P.S.

Research Center of Neurology

Shamtieva K.V.

Research Center of Neurology

Tsypushtanova M.M.

Research Center of Neurology

Trubitsyna V.V.

Research Center of Neurology

Gnedovskaya E.V.

Research Center of Neurology

Received:

10.05.2023

Accepted:

17.05.2023

Close metadata

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