Yang SP, Bae DG, Kang HJ, Gwag BJ, Gho YS, Chae CB.
Co-accumulation of vascular endothelial growth factor with beta-amyloid in the brain of patients with Alzheimer's disease.
Neurobiol Aging. 2004 Mar;25(3):283-90.
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Dr. Yang and colleagues report finding VEGF coaccumulates markedly with amyloid plaques in the brain of patients with AD. Their study shows VEGF directly binds to Aβ peptides with high affinity and specificity and is slowly released from the coaggregated complex. They conclude that steady deposition of VEGF in the amyloid plaques most likely results from cerebral hypoperfusion during the AD state due to a deficiency of available VEGF. This is a reasonable assumption that requires further studies to substantiate. It is now well accepted that AD is associated with chronic brain hypoperfusion but it is not widely known that this hypoperfusion state is already present at the mild cognitive impairment (MCI) stage where the density of senile plaques and cognitive symptoms are insufficient to provide a diagnosis of AD. In fact, dozens of neuroimaging studies showing regional brain hypoperfusion during MCI will be reported at the upcoming 9th Alzheimer Conference on AD (click on Program Schedule then click on Program Navigator and “search” for hypoperfusion or blood flow).
How to interpret Yang et al.’s findings?
Previous studies have shown that VEGF immunoreactivity is increased in reactive astrocytes in AD neocortex (Kalaria et al., 1998). Could it then be said that during astrocytosis in AD, VEGF forms in glial cells as a result of a need for angiogenesis or neuroprotection? Perhaps, but since VEGF has also been found in choroid plexus in AD and ganglion cells in diabetic retinas and in a number of non-dementia disease states, we can only conclude that expression of this angiogenic growth factor appears ubiquitous during pathological states involving its production from macrophages, neutrophils and vascular endothelial cells. VEGF’s relationship with its mediator nitric oxide (de la Torre et al., 2000) and its possible role in the upregulation of eNOS expression and NO production in angiogenesis suggests that during ischemia-hypoxia, this cytokine reacts by attempting to increase blood flow either through angiogenesis or NO activated vasodilation. What seems clear is that the role of VEGF in AD is a virtually unexplored research avenue and one that could provide important clues on the pathogenesis of AD and more importantly, in the long search for better treatments of this dementia.
For these reasons, Yang et al.’s findings are important in attempting to clarify the cellular mechanisms and the molecular regulation of angiogenesis in the pathological state.