Co-accumulation of vascular endothelial growth factor with β-amyloid in the brain of patients with Alzheimer’s disease

• Published in: Neurobiology of aging 2004-03, Vol.25 (3), p.283-290
• Main Authors: Yang, Seung-Pil, Bae, Dong-Goo, Kang, Hyo Jung, Gwag, Byoung Joo, Gho, Yong Song, Chae, Chi-Bom
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer’s disease; Amyloid beta-Peptides - metabolism; Biological and medical sciences; Brain - blood supply; Brain - metabolism; Brain - physiopathology; Cerebral Arteries - metabolism; Cerebral Arteries - pathology; Cerebral Arteries - physiopathology; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Hypoperfusion; Macromolecular Substances; Medical sciences; Neovascularization, Physiologic - physiology; Neurology; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Protein Binding - physiology; Senile plaque; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; β-amyloid
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(03)00111-8

Alzheimer’s disease (AD) is accompanied by the progressive deposition of β-amyloid (Aβ) 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 Aβ has not been established. Here, we show that VEGF is co-localized with Aβ plaques in the brains of patients with AD. In vitro experiments show that VEGF binds to Aβ with high affinity ( K D≈50 pM). VEGF is co-aggregated with Aβ without any apparent effect on the rate of aggregation, strongly binds to pre-aggregated Aβ, 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.