Role of vascular endothelial growth factor (VEGF) in Alzheimer's disease

Peter Carmeliet, MD, PhD
Flanders Interuniversity Institute (Leuven, Belgium)
Year Awarded:
Grant Duration:
April 1, 2003 to March 31, 2005
Alzheimer's Disease
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Role of vascular endothelial growth factor (VEGF) in Alzheimer's disease


Characteristic of Alzheimer's disease are the accumulation of “tangles” and “plaques” made from protein fragments in areas of brain damage. Although the brain blood flow is often lower in patients with AD than in healthy individuals, and cerebrovascular abnormalities are often found in AD, the possible role of vascular lesions and brain perfusion in the pathogenesis of AD has received only limited attention. If one considers that the brain is particularly vulnerable to suboptimal oxygen and glucose delivery, it is conceivable that vascular abnormalities and reduced cerebral blood flow could lead to the suboptimal delivery of oxygen and nutritients to neuronal tissue, resulting in tissue ischemia and neurodegenerative processes. Vascular endothelial growth factor (VEGF) is a key player in the formation of new blood vessels. Because the expression of VEGF is strongly increased under low oxygen conditions, one could anticipate that VEGF will then stimulate new blood vessel formation, resulting in the restoration of tissue perfusion and oxygenation. To evaluate the importance of cerebral blood flow in AD, Dr. Carmeliet and his colleagues are working to develop new mouse lines. In addition to VEGF´s essential role in the vascular system, it also appears to have direct “neurotrophic” and “neuroprotective” effects. The relative importance of impaired perfusion and the of loss of neuroprotection by impaired VEGF expression, however, still needs to be analyzed. It is hoped that the results of this study will help define targets or effector molecules that may be used in therapies to delay or halt the progression of AD.


Storkebaum, E. and Carmeliet, P. (2004) VEGF: a critical player in neurodegeneration. J Clin Invest. 113(1):14-8.  

Lambrechts, D., Storkebaum, E., and Carmeliet, P. (2004) VEGF: necessary to prevent motoneuron degeneration, sufficient to treat ALS? Trends Mol Med. 10(6):275-282.  

Storkebaum, E., Lambrechts, D., and Carmeliet, P. (2004) VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 26(9):943-954.  

Azzouz, M., Ralph, G.S., Storkebaum, E., Walmsley, L.E., Mitrophanous, K.A.,Kingsman, S.M., Carmeliet, P., and Mazarakis, N.D. (2004) VEGF delivery with retrogradely transported lentivector prolongs survivial in a mouse ALS model. Nature. 429(6990):413-417. [Alzforum Recommended Paper]  

Van Den Bosch, L., Storkebaum, E., Vleminckx, V., Moons, L., Vanopdenbosch, L., Scheveneels, W., Carmeliet, P., and Robberecht, W. (2004) Effects of vascular endothelial growth factor (VEGF) on motor neuron degeneration. Neurobiol Dis. 17(1):21-28.  

Storkebaum, E., Lambrechts, D., Moreno-Murciano, M.P., Oh, H., Van Damme, P., Rutten, B., Appelmans, S., Man, W.Y., De Mol, M., Wyns, S., Manka, D., Vermeulen, K., Van Den Bosch, L., Mertens, M., Schmitz, C., Robberecht, W., Conway, E.M., Collen, D., Dewerchin, M., Moons, L., and Carmeliet, P. (2005) Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat. Neuroscience. 8(1):85-92.  

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