| Gene |
[FLT1](/genes/flt1) |
| UniProt |
P17948 |
| PDB |
5E32, 1FLV |
| Mol. Weight |
180 kDa (full-length), 100 kDa (sVEGFR1/sFlt1) |
| Localization |
Cell surface (endothelial cells), soluble form (sFlt1) |
| Family |
VEGFR family (RTK) |
| Diseases |
[Alzheimer's Disease](/diseases/alzheimers), [Vascular Dementia](/diseases/vascular-dementia) |
FLT1 (Vascular Endothelial Growth Factor Receptor 1, VEGFR1) is a receptor tyrosine kinase that primarily binds VEGF-A, VEGF-B, and PlGF. It is expressed on endothelial cells and plays crucial roles in angiogenesis, vascular development, and neurovascular function. In the brain, FLT1 is involved in blood-brain barrier maintenance and has been implicated in Alzheimer's disease pathogenesis.
FLT1 is a type I transmembrane receptor with characteristic receptor kinase architecture:
- Extracellular domain: Seven immunoglobulin-like domains for ligand binding
- Transmembrane domain: Single pass helix
- Cytoplasmic domain: Tyrosine kinase domain with kinase insert
A soluble form (sFLT1 or sVEGFR1) is generated by alternative splicing, acting as a VEGF antagonist.
In the nervous system:
- Angiogenesis: Primary receptor for VEGF-mediated blood vessel formation
- Blood-brain barrier maintenance: Regulates endothelial tight junction integrity
- Neuroprotection: VEGF-FLT1 signaling promotes neuronal survival
- Neural development: Involved in developmental angiogenesis in the brain
- sFLT1 levels elevated in AD patient CSF and plasma
- sFLT1 acts as endogenous VEGF inhibitor, reducing vascular health
- FLT1 polymorphism associated with AD risk
- Implicated in vascular dysfunction and reduced cerebral blood flow in AD
- Role in Aβ-induced angiogenic dysfunction
- Direct involvement in cerebrovascular disease pathogenesis
- Altered VEGF/FLT1 signaling in small vessel disease
- FLT1 expressed on microglia under inflammatory conditions
- Mediates VEGF-induced inflammatory responses
Targeting FLT1 signaling:
- VEGF-FLT1 agonists to improve cerebral blood flow
- sFLT1 neutralization to restore VEGF signaling
- Small molecule FLT1 inhibitors for anti-angiogenic therapy in CAA
- sFLT1 in Alzheimer's disease (Alzheimer's & Dementia, 2020)
- FLT1 and vascular dysfunction in AD (Lorenz et al., 2018)
- VEGF-FLT1 signaling in neurodegeneration (Ruiz de Alonso et al., 2022)