سطح بیان فاکتور رشد اندوتلیال عروقی در هیپوکامپ با اختلال شناختی در بیماران مبتلا به بیماری آلزایمر همراه است

Although the enhanced expression of vascular endothelial growth factor (VEGF) in the brains of patients with Alzheimer's disease (AD) has been reported, the functional significance of VEGF level in the progression of AD is still unclear. We examined the VEGF expression in the hippocampus of patients with AD at different stages of progression by Western blot analysis, and found that the VEGF189 isoform (VEGF189) was barely detectable in normal hippocampus, but significantly increased at the early stage of patients with AD. VEGF189 was decreased with advancing stages of AD. Immunostaining shows that VEGF was significantly increased in the cells in the CA1, CA3, and dentate gyrus regions of hippocampus and layers III and V of entorhinal cortex of patients with AD, compared with normal brain. Confocal images show that VEGF was predominantly expressed in neurons and astrocytes in the hippocampus and entorhinal cortex of patients with AD. Our data suggest that VEGF level is associated with progressive loss of cognitive function in patients with AD.

Several growth factors have been implicated in the pathogenesis of Alzheimer's disease (AD). One of them is vascular endothelial growth factor (VEGF). Genetic analysis indicates that single nucleotide polymorphisms within the VEGF gene promoter region confer greater risk for AD, vascular dementia, and frontotemporal lobal degeneration, but others could not repeat these findings (Chapuis et al., 2006). Abnormal expression level of VEGF is also observed in patients with AD. For example, enhanced VEGF immunoreactivity is observed in reactive astrocytes in the neocortex and large intraparenchymal vessels and capillaries of subjects with AD compared with elderly control subjects. AD is often accompanied by reactive astrogliosis and microglia activation, suggesting a role of VEGF in neurodegenerative processes associated with AD. In addition, VEGF is also heavily accumulated and colocalized with amyloid-beta (Aβ) plaques in the brains of patients with AD. Consistently, the serum VEGF levels in patients with AD are significantly lower than in control subjects, which could be because of the continuous deposition of VEGF in the amyloid plaques (Mateo et al., 2007). Decreased serum VEGF levels are associated with AD in a dose-dependent manner, the lower third of serum VEGF levels being associated with a 5-fold increased risk for AD when compared with the upper third (Mateo et al., 2007). However, other studies show that VEGF level is elevated in the cerebrospinal fluid and the peripheral blood of patients with AD (Corsi et al., 2011). VEGF in cerebrospinal fluid is correlated with the severity of cognitive impairment. Therefore, whether VEGF is increased in patients with AD remains a matter of debate, and the functional significance of VEGF level in the pathogenesis and progression of AD is still unclear. In the current study, we examined the VEGF expression levels in the hippocampus of patients with AD at different stages of progression by Western blot analysis, and found that the VEGF189 isoform (VEGF189) level is associated with progressive loss of cognitive function in patients with AD. Immunostaining confirms increased VEGF expression in the neurons and astrocytes in the hippocampus and entorhinal cortex of AD brain.