Pulmonary arterial hypertension–associated cerebellar impairment extends evidence linking cardiometabolic and neurodegenerative diseases

Growing evidence shows that the risk of cognitive impairment is increased across a range of metabolic and cardiovascular diseases, but underlying mechanisms remain poorly understood. One possibility involves activation of microglia, a glial cell type of the central nervous system with morphological and transcriptional features comparable to resident macrophages in other tissues that plays specialized roles in supporting neuronal and brain function. Combining clinical investigation in pulmonary arterial hypertension (PAH) cohorts with mouse model and microglial cell culture studies, a study by Okawa, Shi, and colleagues in this issue of the JCI adds compelling, albeit indirect, evidence linking impaired lysosomal lipid handling in both endothelial cells and microglia to a specific neurological disorder associated with PAH. The findings open opportunities for understanding how cardiopulmonary disease predisposes to neurodegeneration.