Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and β-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain

The up‐regulation of the angiogenic vascular endothelial growth factor (VEGF) in brains of Alzheimer patients in close relationship to β‐amyloid (Aβ) plaques, suggests a link of VEGF action and processing of the amyloid precursor protein (APP). To reveal whether VEGF may affect APP processing, brain slices derived from 17‐month‐old transgenic Tg2576 mice were exposed with 1 ng/ml VEGF for 6, 24, and 72 h, followed by assessing cytosolic and membrane‐bound APP expression, level of both soluble and fibrillar Aβ‐peptides, as well as activities of α‐ and β‐secretases in brain slice tissue preparations.

[1]  A. Drzezga,et al.  In vivo characterization of endothelial cell activation in a transgenic mouse model of Alzheimer’s disease , 2006, Angiogenesis.

[2]  J. LaManna,et al.  Vascular endothelial growth factor in Alzheimer's disease and experimental cerebral ischemia. , 1998, Brain research. Molecular brain research.

[3]  W. Markesbery,et al.  Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. , 1997, JAMA.

[4]  R. Kraftsik,et al.  Cerebral Hypoperfusion Generates Cortical Watershed Microinfarcts in Alzheimer Disease , 2002, Stroke.

[5]  K. Jellinger,et al.  Amyloid β peptide 1–42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology , 2004, Acta Neuropathologica.

[6]  P. Hof,et al.  Brain Microvascular Changes in Alzheimer's Disease and Other Dementias a , 1997, Annals of the New York Academy of Sciences.

[7]  Y. T. Wang,et al.  Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology , 2009, The Journal of Neuroscience.

[8]  J. C. de la Torre,et al.  Can disturbed brain microcirculation cause Alzheimer's disease? , 1993, Neurological research.

[9]  D. Royall,et al.  Alzheimer disease as a vascular disorder: nosological evidence. , 2002, Stroke.

[10]  W. Poewe,et al.  Ischemic stress induces deposition of amyloid beta immunoreactivity in human brain. , 1995, Acta neuropathologica.

[11]  M. Bernaudin,et al.  Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. , 2000, The American journal of pathology.

[12]  J. Lambert,et al.  Association study of the vascular endothelial growth factor gene with the risk of developing Alzheimer's disease , 2006, Neurobiology of Aging.

[13]  P. Carvey,et al.  Evidence of angiogenic vessels in Alzheimer’s disease , 2009, Journal of Neural Transmission.

[14]  R. Schliebs,et al.  Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology , 2004, International Journal of Developmental Neuroscience.

[15]  S. Younkin,et al.  Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice , 1996, Science.

[16]  P. Carmeliet,et al.  Role and therapeutic potential of VEGF in the nervous system. , 2009, Physiological reviews.

[17]  P. R. Hof,et al.  Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders , 1994, Acta Neuropathologica.

[18]  O. Bugiani,et al.  Thickening of the basement membrane of cortical capillaries in Alzheimer's disease , 2004, Acta Neuropathologica.

[19]  Anders Wallin,et al.  Increased intrathecal levels of the angiogenic factors VEGF and TGF-β in Alzheimer’s disease and vascular dementia , 2002, Neurobiology of Aging.

[20]  Yong Song Gho,et al.  Co-accumulation of vascular endothelial growth factor with β-amyloid in the brain of patients with Alzheimer’s disease , 2004, Neurobiology of Aging.

[21]  T. Berzin,et al.  Microvascular injury and blood–brain barrier leakage in Alzheimer's disease , 2007, Neurobiology of Aging.

[22]  S. Younkin,et al.  Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. , 2001, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[24]  N. Patel,et al.  Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis , 2004, Neuroscience Letters.

[25]  V. Camus,et al.  Endothelial dysfunction: A potential therapeutic target for geriatric depression and brain amyloid deposition in Alzheimer's disease? , 2009, Current opinion in investigational drugs.

[26]  James A. Mortimer,et al.  Brain Infarction and the Clinical Expression of Alzheimer Disease-Reply , 1997 .

[27]  T. Strandberg.  Alzheimer's disease and angiogenesis , 2003, The Lancet.

[28]  V. Fischer,et al.  Altered angioarchitecture in selected areas of brains with Alzheimer's disease , 2004, Acta Neuropathologica.

[29]  D. Coppola,et al.  Inhibition of angiogenesis by Abeta peptides. , 2004, Angiogenesis.

[30]  Mikio Shoji,et al.  Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease , 2001, The Journal of Neuroscience.

[31]  R. Kalaria.  The role of cerebral ischemia in Alzheimer’s disease , 2000, Neurobiology of Aging.

[32]  N. Patel,et al.  Inhibition of angiogenesis and tumor growth by and ?-secretase inhibitors , 2005 .

[33]  R. Kalaria,et al.  Increased collagen content of cerebral microvessels in Alzheimer's disease , 1995, Brain Research.

[34]  F. Sun,et al.  Molecular and cellular mechanisms of neuroprotection by vascular endothelial growth factor , 2005, Journal of neuroscience research.

[35]  R. Kalaria.  Small Vessel Disease and Alzheimer’s Dementia: Pathological Considerations , 2002, Cerebrovascular Diseases.

[36]  G C Roman,et al.  Brain infarction and the clinical expression of Alzheimer disease. , 1997, JAMA.

[37]  D. Soffer.  Cerebral amyloid angiopathy--a disease or age-related condition. , 2006, The Israel Medical Association journal : IMAJ.

[38]  P. Grammas,et al.  Angiogenic proteins are expressed by brain blood vessels in Alzheimer's disease. , 2006, Journal of Alzheimer's disease : JAD.

[39]  M. Neeman,et al.  Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes , 1995, Molecular and cellular biology.

[40]  R. Schliebs,et al.  Muscarinic acetylcholine receptor inhibition in transgenic Alzheimer-like Tg2576 mice by scopolamine favours the amyloidogenic route of processing of amyloid precursor protein , 2006, International Journal of Developmental Neuroscience.

[41]  Stanley J. Wiegand,et al.  Vascular-specific growth factors and blood vessel formation , 2000, Nature.

[42]  B. Pappas,et al.  Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion , 2000, Neurobiology of Aging.

[43]  P. Luiten,et al.  Cerebral microvascular pathology in aging and Alzheimer's disease , 2001, Progress in Neurobiology.

[44]  R. Vassar,et al.  Linking vascular disorders and Alzheimer's disease: Potential involvement of BACE1 , 2009, Neurobiology of Aging.

[45]  D. Mann,et al.  Quantitative changes in cerebral cortical microvasculature in ageing and dementia , 1986, Neurobiology of Aging.

[46]  V. Bigl,et al.  Astrocytic expression of the Alzheimer's disease β‐secretase (BACE1) is stimulus‐dependent , 2003, Glia.

[47]  W. Lukiw,et al.  Angiogenic signaling in Alzheimer's disease , 2004, Neuroreport.

[48]  N. Ferrara,et al.  The biology of VEGF and its receptors , 2003, Nature Medicine.

[49]  D. Ingber,et al.  Inhibition of angiogenesis. , 1992, Seminars in cancer biology.

[50]  N. Patel,et al.  Inhibition of angiogenesis and tumor growth by beta and gamma-secretase inhibitors. , 2005, European journal of pharmacology.

[51]  P. Hedera,et al.  Differential degeneration of the cerebral microvasculature in Alzheimer's disease. , 1995, Neuroreport.

[52]  Luz Claudio,et al.  Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients , 1995, Acta Neuropathologica.

[53]  W. Risau,et al.  Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[54]  H. Vinters,et al.  Brain Parenchymal and Microvascular Amyloid in Alzheimer's Disease , 1996, Brain pathology.

[55]  J. C. Torre,et al.  Pathophysiology of Neuronal Energy Crisis in Alzheimer’s Disease , 2008, Neurodegenerative Diseases.

[56]  M. Mullan,et al.  β-Amyloid-mediated vasoactivity and vascular endothelial damage , 1996, Nature.

[57]  F. Crawford,et al.  Vasoactive effects of A beta in isolated human cerebrovessels and in a transgenic mouse model of Alzheimer's disease: role of inflammation. , 2003, Neurological research.

[58]  H. Figueiredo,et al.  Thrombin Induces Surface and Intracellular Secretion of Amyloid Precursor Protein from Human Endothelial Cells , 1999, Thrombosis and Haemostasis.

[59]  M. Mullan,et al.  beta-Amyloid-mediated vasoactivity and vascular endothelial damage. , 1996, Nature.