Co-accumulation of vascular endothelial growth factor with beta-amyloid in the brain of patients with Alzheimer's disease.
Alzheimer's disease (AD) is accompanied by the progressive deposition of beta-amyloid (Abeta) in both senile plaques and cerebral blood vessels, loss of central neurons, and vessel damage. Cerebral hypoperfusion is one of the major clinical features in AD and likely plays a critical role in its pathogenesis. In addition to its major roles in angiogenesis, vascular endothelial growth factor (VEGF) has neurotrophic and neuroprotective effects. VEGF is an ischemia-inducible factor and increased expression of VEGF often occurs in AD. Although the presence of VEGF immunoreactivity in the AD brain has been described previously, the direct interaction of VEGF with Abeta has not been established. Here, we show that VEGF is co-localized with Abeta plaques in the brains of patients with AD. In vitro experiments show that VEGF binds to Abeta with high affinity (K(D) approximate to 50 pM). VEGF is co-aggregated with Abeta without any apparent effect on the rate of aggregation, strongly binds to pre-aggregated Abeta, and is very slowly released from the co-aggregated complex. Continuous deposition of VEGF in the amyloid plaques most likely results in deficiency of available VEGF under hypoperfusion and, thus, may contribute to neurodegeneration and vascular dysfunction in the progression of AD.
Yang
Seung-Pil
SP
Department of Life Science, Division of Molecular and Life Sciences, and Postech Biotech Center, Pohang University of Science and Technology, Pohang, 790-784, South Korea.
Bae
Dong-Goo
DG
Kang
Hyo Jung
HJ
Gwag
Byoung Joo
BJ
Gho
Yong Song
YS
Chae
Chi-Bom
CB
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D046911:Macromolecular Substances; D018919:Neovascularization, Physiologic / Q000502:physiology; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D046911:Macromolecular Substances; D042461:Vascular Endothelial Growth Factor A