Neurovascular Molecular Signatures in Neurodegeneration

A cross-disease single-cell atlas of the human brain neurovascular unit in Alzheimer's, Huntington's and frontotemporal dementia

Interactive companion to a comparative single-cell / single-nucleus RNA-seq study of human brain vascular and perivascular cells across three neurodegenerative diseases: Alzheimer's disease (AD), Huntington's disease (HD) and GRN-related frontotemporal dementia (FTD-GRN). Differential expression versus matched controls was computed per cell type with MAST. A positive log₂ fold-change means higher expression in disease relative to control. The headline finding is a shared neurovascular signature, concentrated in pericytes and capillary endothelium, that converges across all three diseases despite their distinct primary pathologies.

Cell atlas

Harmonized single-nucleus UMAP of the brain neurovascular unit, downsampled to 5,000 nuclei per disease. Colour by cell type, or by condition to see control versus disease. Each disease has its own integrated embedding.

Disease

Colour by

Cell type

Gene search

Search any detected gene (not only DEGs). Absolute expression (default) shows mean expression in control and disease per cell type, scaled to each gene's peak across the three diseases so AD / HD / FTD are comparable, useful for confirming markers. Disease difference shows the disease-versus-control log₂ fold-change (dark outline = FDR ≤ 0.05).

DEGs: ADAMTS9, COL4A1, VEGFC, NAMPT · markers: CLDN5, PDGFRB, RGS5, AQP4, P2RY12, PLP1

View

Scale

Cell-type DEGs

Top differentially expressed genes for a chosen disease and cell type, ranked by fold-change. Click a gene to open it in the search view.

Disease

Cell type

Direction

Cross-disease convergence

Genes dysregulated in the same direction across AD, HD and FTD-GRN define a shared neurodegeneration signature. The Venn shows the overlap of significant DEGs (FDR ≤ 0.05, |log₂FC| ≥ 0.5) for the selected cell type; the lists below are concordant genes (same direction in all three diseases).

Cell type

DEG overlap across diseases

Concordant shared genes (all three diseases)

Pericyte focus

Pericytes carry the strongest convergent signal. Matrix-associated pericytes (M-peri) are selectively depleted across all three diseases, shifting the balance toward transport-type pericytes (T-peri).

M-pericyte proportion: control vs disease

% of pericytes that are matrix-associated (M-peri). Values from the study.

Core matrix-pericyte genes (study Fig. 3D)

M-peri markers (matrix / ECM)

T-peri markers (transport)

Endothelial zonation

Endothelial differential expression resolved by vascular segment (arterial, capillary, venous). Capillary endothelium shows the greatest cross-disease convergence.

Disease

Segment

Direction

Pathway enrichment

Gene Ontology terms enriched among differentially expressed genes, by disease. Bars show fold-enrichment; hover for the adjusted p-value and gene count.

Disease

Scope

Ontology

Pericyte–endothelial signaling

Ligand-receptor communication between pericytes and endothelial cells (CellChat), and how it is remodelled in disease. Extracellular-matrix and adhesion pathways (laminin, collagen, fibronectin, NCAM) are the most consistently altered across all three diseases; other changes are disease-weighted.

Pathway	Class	Cross-disease pattern	Notes

Curated from the study's CellChat analysis (Fig. 4, Supp. Fig. 4). The study reports pathway-level remodeling and disease-weighting rather than a simple per-disease up/down for every pathway. Raw interaction tables can be added to make this section fully data-driven.