Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
https://www.nature.com/articles/s41467-026-75367-0
The brain’s blood vessels and immune cells play important roles in maintaining brain health, but their contribution to neurological disease is not fully understood. This study investigated how cells in the brain respond to three conditions associated with inflammation and vascular dysfunction (blood vessels and circulation affected): Alzheimer’s disease (AD), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and traumatic brain injury (TBI). Researchers used mouse models of these conditions and performed single-cell RNA sequencing (scRNA-seq), a technique that allows scientists to examine gene activity in individual cells. More than 250,000 cells were analysed across different stages of disease, providing a detailed picture of how different brain cell types respond. Transcriptional profiling captures transcriptional cell profiles which provides information about how genetic information is expressed, how proteins are produced, and how cells function. Unexpectedly, the researchers found that most vascular cells (make up the blood and lymphatic vessels), including endothelial cells and vascular smooth muscle cells, showed remarkably stable transcriptional profiles. This was observed even when there was clear disease-related pathology. Although some localised vascular changes occurred following TBI, there was little evidence of widespread changes in gene expression across the brain’s vasculature which is the body’s network of blood vessels. In contrast, microglia, the brain’s immune cells, showed substantial and disease-specific changes in gene expression. Different groups of activated microglia were identified, including disease-associated microglia (DAMs), which expressed genes linked to inflammation and immune responses. Interestingly, microglial responses in late-stage TBI became increasingly similar to those observed in AD. The findings suggest that microglia may be more transcriptionally responsive to neurological damage than vascular cells. The similarities between TBI and AD microglial responses may also help explain why traumatic brain injury can increase susceptibility to later neurodegeneration. Overall, this research provides a valuable molecular resource for understanding how neuroinflammation and the brain’s vasculature interact across different neurological diseases.