Brain extracellular matrix implications in multiple neurological disorders revealed through a meta-analysis of transcriptional changes

Neurological disorders comprise a wide range of illnesses that may affect the central and peripheral nervous systems. Despite their diverse etiologies, many of these disorders present overlapping symptoms. In this study, we sought to generate hypotheses about shared biological mechanisms across neurodegenerative, neuropsychiatric, and neurodevelopmental disorders by analyzing gene expression data and identifying the most consistently dysregulated genes within and between these groups. To provide additional validation, we referenced Genome-Wide Association Studies (GWAS) data, which supported many of the transcriptomic analyses. Our exploratory analysis identified 31 differentially expressed genes shared across these neurological conditions, compared to healthy controls. These genes were significantly enriched in brain extracellular matrix (ECM) pathways, and dysregulation of ECM genes was evident separately in each of the three disorder categories. Notably, SST (Somatostatin), involved in modulating cortical circuits and cognitive function, was the most frequently reported dysregulated gene shared among the three categories of disorders. Furthermore, we observed consistent patterns suggesting that GFAP (glial fibrillary acidic protein), a key intermediate filament in mature astrocytes and a well-known marker of reactive astrocytes, and IFITM3 (interferon-induced transmembrane protein 3), a crucial component of the first-line antiviral defense, were on average the most frequently reported genes among the studied disorders. Our study's core findings indicated that shared molecular features may exist across neurological disorders, emphasizing significant differences in the ECM of the central nervous system (CNS) between health and disease. • Meta-analysis reveals shared mechanisms across seven brain disorders. • Key molecular changes in brain disorders extend beyond neuronal dysfunction. • Extracellular matrix gene dysregulation is a hallmark feature across disorders. • Gene expression changes in early development processes are shared across disorders. • SST, GFAP , and IFITM3 showed consistent dysregulation across multiple disorders.