Development Of Human Neurovascular Unit 
Atlas For Alzheimer's Patients

The NVUAtlas reveals extensive disruption of vascular homeostasis, sex-specific molecular responses, and altered intercellular signaling across the neurovascular unit in Alzheimer’s patients. This integrated atlas leverages existing datasets to support systematic investigation of neurovascular unit dysfunction in the pathogenesis of Alzheimer’s disease.

Introduction: 

The neurovascular unit (NVU) includes endothelial cells, pericytes, astrocytes, and neurons. The endothelial cells lining  the capillary lumen form the blood-brain barrier (BBB), which drives neurovascular coupling and regulates molecular exchange between the circulation and brain. The uncoupling of NVU is being recognized as an early contributor to Alzheimer’s disease (AD), with BBB dysfunction often preceding neurodegeneration1,2. The human NVU Atlas leverages existing datasets to advance systematic investigation of the NVU dysfunction and intercellular interactions in AD.

Methods:

Prefrontal cortex 
11 snRNA-seq cohorts 
748  donors, 4.25M nuclei

scVI3 integration
Consensus annotation 
(KNN, SVM, scANVI, scGPT) 

DE (NEBULA4)

Pathway enrichment

Ligand-receptor inference

Results:

Vascular cells show the most extensive changes

Sex-specific changes in NVU intercellular signaling 

Conclusions: