Study on the pathogenesis of vascular dementia by gene expression regulatory network

Abstract

Vascular dementia (VaD) is the second largest type of dementia in the world after Alzheimer’s disease, characterized by selective loss of neurons caused by cerebrovascular disease, dysfunction of cortical subcortical circuits, and cognitive domain specific damage. This article systematically analyzes some gene expression regulation issues in VaD pathogenesis from five dimensions: abnormal gene expression profile, epigenetic modification abnormality, transcription factor (TF) cascade regulation, non coding RNA (ncRNA) regulatory axis disorder, and gene environment interaction. For the first time, the “Dynamic Imbalance Theory of Gene Regulation Network” (DIGRN) is proposed. By integrating transcriptomics, epigenomics, proteomics, and clinical sample analysis, the key roles of abnormal DNA methylation, histone modification imbalance, transcription factor cascade activation, miRNA lncRNA regulatory axis disruption, and synergistic effects of environmental factors in VaD pathology were revealed. The DIGRN theory provides a new framework for early diagnosis, molecular typing, and targeted intervention of VaD. Its clinical translation prospects involve epigenetic drug development, ncRNA biomarker screening, and construction of gene environment interaction risk prediction models.