Table 1 Biological pathways and transcriptomic profiles associated with Alzheimer’s disease in the vascular cells of the NVU and GVU

Endothelial cells

Angiogenesis

Vascular homoeostasis

CLDN5 ↑, ERG ↑, FLT1 ↑, VWF ↑, ANGPT2 ↑, INSR ↑, ETS1 ↑

ENG ↑, TGM2 ↑, STAT3 ↑, HIF1A ↑, FGF2 ↑

VEGFA ↓, VEGFR2↓, EGFR ↓, SPRED2↓

[33, 62,63,64,65, 82,83,84,85, 139]

cell proliferation and endothelial damage

EBF1↓, TSHZ2 ↑,

VWF ↑, ABCG2 ↑, ABCB1 ↑

PGRMC1↓

[99, 100]

Immune response

inflammation

HLA-E ↑, IL6 ↑, IL6R ↑,

CR1↓, PLCG2↓, TEK ↓,

[63, 65]

antigen presenting machinery

B2M ↑, HLA-E↑

[82]

interferon-γ signaling

IFNγ ↑

[63, 64]

COVID-19-response

SARS-CoV-2 docking receptors

NRP1↑, BSG↑

[167]

SARS-CoV-2 host factors

BSG ↑, FURIN↑

[167]

antiviral defense genes

LY6E ↑, IFITM2↑, IFITM3↑, IFNAR1 ↑

[167]

BBB integrity

BBB integrity

CTNNB1↑

[94]

amyloid-beta clearance (p-glycoprotein)

SCARB1 ↑,

ATP10A ↓, ABCB1 ↓, PICALM ↓

[65, 94, 99, 139]

Synaptic Signaling/ ECM Organization

protein folding, cytoskeletal remodeling and intracellular trafficking

HSP90AA1↑, HSPH1↑, HSPA1A ↑, JSPB1 ↑, COL4A1 ↑, INPP5D ↑, CD2AP ↑, ARL15↑,

MYRIP ↓, PICALM ↓

[94, 63,64,65, 139]

Mural cells and fibroblasts

Pericytes

Angiogenesis/

BBB integrity

Dysregulated blood flow, injury & oxidative stress, inflammation,

PLCG2↑, BACH1↑,

SLC12A7 ↑, SLC6A12 ↑, SLC19A1 ↑, COL4A1 ↑, CDH6 ↑, SNTB1↑, RIPK2↑, PDGFRβ ↑,

EGFR ↓, MEF2C ↓

[33, 62,63,64,65, 139]

Synaptic Signaling/

ECM remodeling

synaptic transmission, cytoskeleton remodeling and contraction, growth factor

FLT1 ↑, SMAD3 ↑, STAT3 ↑, GRM8 ↑

ADAMTS1 ↑, ADAMTS4 ↑, ADAM10, FERMT2 ↑, AGRN ↑, TAGLN ↑

SLC6A1 ↓, MYO1B ↓, DMD ↓

[33, 63,64,65, 139]

Cholesterol regulation

HDL metabolism

APOD ↑, SCARB1 ↑

[65]

Fibroblasts

CNS Injury repair/

ECM remodeling

fibrotic scars formation, structural integrity

COL1 ↑

SPTBN1↓, LAMC1↓

[65, 139]

Immune Response/

Cell Signaling

Transcriptional regulation, HDL metabolism, inflammation

TAGLN ↑, ABCA1↑, FHL2, ↑, HESX1↑, IL34 ↑, PLCG2↑, APOE ↑,

ABCA9 ↑, CEMIP ↑, C7 ↑

SPRED2↓, DAB2IP ↓, DTX2↓, BCL2L1↓,

FBLN1

[62,63,64,65, 139]

SMCs

ECM-organization/

Cholesterol metabolism

Inflammation, cytoskeletal remodeling, amyloid-beta clearance,

APOE ↑, ADAMTS1 ↑, ADAMTS4 ↑, FERMT2 ↑,

PFDN1 ↓

[63, 65]