![]() The authors have declared no competing interest. Our work unravels the molecular basis of the human brain vasculature, informing our understanding of overall brain health, disease, and therapy. Many are microglia-specific in mice, suggesting an evolutionary transfer of AD risk to human vascular cells. Vascular GWAS genes map to endothelial protein transport, adaptive immune, and ECM pathways. With an expanded survey of brain cell types, we find that 30 of the top 45 AD GWAS genes are expressed in the human brain vasculature, confirmed in situ. In AD, we observe a selective vulnerability of ECM-maintaining pericytes and gene expression patterns implicating dysregulated blood flow. ![]() We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization and define perivascular versus meningeal fibroblast specialization. We describe the principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum but discover that many zonation and cell-type markers differ between species. We identify brain region-enriched pathways and genes divergent between humans and mice, including those involved in disease. Here, we develop Vessel Isolation and Nuclei Extraction for Sequencing (VINE-seq) to profile the major human brain vascular and perivascular cell types through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 17 control and Alzheimer’s disease (AD) patients. This model is used to address dispersion and delay of the arterial input function (AIF) at different levels of the vascular structure and to estimate the local AIF in DCE images. The ventricles of the brain contain vascular choroid plexuses, from. In this paper, we introduce a novel model of the brain vascular system, which is developed based on laws of fluid dynamics and vascular morphology. Yet, no molecular atlas of the human brain vasculature exists. The space between the arachnoid and the pia mater, the subarachnoid space, contains CSF. The human brain vasculature is of vast medical importance: its dysfunction causes disability and death, and the specialized structure it forms-the blood-brain barrier-impedes treatment of nearly all brain disorders.
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