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Angiogenic Mediators and the Pathogenesis of Alzheimer’s Disease

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Therapeutic Angiogenesis for Vascular Diseases

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Abstract

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that affects more than 5 million people in the United States. At present, no disease-modifying drugs are available; new therapeutic approaches are desperately needed. Considerable evidence links vascular dysfunction, vascular risk factors, and the pathogenesis of AD. Data are emerging to support the idea that factors and processes characteristic of angiogenesis are found in AD brain. Genome-wide expression profiling in the AD brain has identified a marked upregulation of genes that promote angiogenesis. Epidemiological studies suggest that some drugs purported to have beneficial effects in AD inhibit angiogenesis. Hypoxia is known to stimulate angiogenesis as well as contribute to the clinical and pathological manifestations of AD. Angiogenesis inhibitors may represent an important and unexplored class of therapeutic drugs for AD. The cerebral microcirculation could be a new target for therapeutic intervention in AD. Identification of “vascular activation” as a target in AD would stimulate translational investigations in this newly defined area and may lead to novel therapeutic approaches for the treatment of this devastating disease.

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References

  • Akiyama H, Ikeda K, et al. (1992) Thrombin accumulation in brains of patients with Alzheimer’s disease. Neurosci Lett 46:152–154.

    Article  Google Scholar 

  • Alkam T, Nitta A, et al. (2008) Restraining tumor necrosis factor-alpha by thalidomide prevents the amyloid-beta-induced impairment of recognition memory in mice. Behav Brain Res 189:100–106.

    Article  PubMed  CAS  Google Scholar 

  • Alzheimer’s Association website http://www.alz.org

  • Araki K, Miyakawa T, et al. (1991) Ultrastructure of senile plaque using thick sections in the brain with Alzheimer’s disease. Jpn J Psychiatry Neurol 45:85–89.

    PubMed  Google Scholar 

  • Balcells M, Wallins JS, et al. (2008) Amyloid beta toxicity dependent upon endothelial cell state. Neurosci Lett 441:319–322.

    Article  PubMed  CAS  Google Scholar 

  • Beher D, Graham SL (2005) Protease inhibitors as potential disease-modifying therapeutics for Alzheimer’s disease. Expert Opin Investig Drugs 14:1385–1409.

    Article  PubMed  CAS  Google Scholar 

  • Bell RD, Zlokovic BV (2009) Neurovascular mechanism and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 118:103–113.

    Article  PubMed  CAS  Google Scholar 

  • Bertolino P, Deckers M, et al. (2005) Transforming growth factor-beta signal transduction in angiogenesis and vascular disorders. Chest 128:585S–590S.

    Article  PubMed  CAS  Google Scholar 

  • Bicknell R, Harris AL (2004) Novel angiogenic signaling pathways and vascular targets. Annu Rev Pharmacol Toxicol 44:219–238.

    Article  PubMed  CAS  Google Scholar 

  • Boscolo E, Folin M, et al. (2007) Beta amyloid angiogenic activity in vitro and in vivo. Int J Mol Med 19:581–587.

    PubMed  CAS  Google Scholar 

  • Bourasset F, Ouellet M, et al. (2009) Reduction of the cerebrovascular volume in a transgenic mouse model of Alzheimer’s disease. Neuropharmacology. [Epub ahead of print].

    Google Scholar 

  • Breitner JC, Welsh KA, et al. (1995) Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging 16:523–530.

    Article  PubMed  CAS  Google Scholar 

  • Buee L, Hof PR, et al. (1992) Immunohistochemical identification of thrombospondin in normal human brain and in Alzheimer’s disease. Am J Pathol 141:783–788.

    PubMed  CAS  Google Scholar 

  • Buee L, Hof PR, et al. (1994) Pathological alterations of the cerebral microvasculature in Alzheimer’s disease and related dementing disorders. Acta Neuropathol 87:469–480.

    Article  PubMed  CAS  Google Scholar 

  • Buee L, Hof PR, et al. (1997) brain microvascular changes in Alzheimer’s disease and other dementias. Ann NY Acad Sci 826:7–24.

    Article  PubMed  CAS  Google Scholar 

  • Claudio L (1996) Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer’s disease patients. Acta Neuropathol 91:6–14.

    Article  PubMed  CAS  Google Scholar 

  • Christov A, Ottman T, et al. (2008) Structural changes in Alzheimer’s disease brain microvessels. Current Alz Res 5:392–395.

    Article  CAS  Google Scholar 

  • Crisby M, Carlson LA, et al. (2002) Statins in the prevention and treatment of Alzheimer’s disease. Alzheimer Dis Assoc Disord 16:131–136.

    Article  PubMed  CAS  Google Scholar 

  • Deininger MH, Fimmen BA (2002) Aberrant neuronal and paracellular deposition of endostatin in brains of patients with Alzheimer’s disease. J Neurosci 22:10621–10626.

    PubMed  CAS  Google Scholar 

  • Del Bo R, Ghezzi S, et al. (2009) VEGF genetic variability is associated with increased risk of developing Alzheimer’s disease. J Neurol Sci [Epub ahead of print].

    Google Scholar 

  • de la Torre JC (2002) Alzheimer disease as a vascular disorder: nosological evidence. Stroke 33:1152–1162.

    Article  Google Scholar 

  • de la Torre JC (2009) Chapter 3 cerebrovascular and cardiovascular pathology in Alzheimer’s disease. Int Rev Neurobiol 84:35–48.

    Article  PubMed  CAS  Google Scholar 

  • de la Torre JC, Mussivand T (1993) Can a disturbed brain microcirculation cause Alzheimer’s disease? Neurol Res 15:146–153.

    PubMed  Google Scholar 

  • Dorheim MA, Tracey WR, et al. (1994) Nitric oxide is elevated in Alzheimer’s brain microvessels. Biochem Biophys Res Comm 205:659–665.

    Article  PubMed  CAS  Google Scholar 

  • Dulak J, Loboda A, et al. (2005) Atorvastatin affect several angiogenic mediators in human endothelial cells. Endothelium 12:233–241.

    Article  PubMed  CAS  Google Scholar 

  • Dupuy E, Habib A, et al. (2003) Thrombin induces angiogenesis and vascular endothelial growth factor expression in human endothelial cells: possible relevance to HIF-1α. J Thromb Haemost 1:1096–1102.

    Article  PubMed  CAS  Google Scholar 

  • Edelber JM, Reed MJ (2003) Aging and angiogenesis. Front Biosci 8:s1199–s1209.

    Article  Google Scholar 

  • Farkas E, De Vos RA, et al. (2000) Are Alzheimer’s disease, hypertension, and cerebrocapillary damage related? Neurobiol Aging 21:235–243.

    Article  PubMed  CAS  Google Scholar 

  • Feldstein CA (2008) Statins as antihypertensives. Recent Pat Cardiovasc Drug Discov 3:92–97.

    Article  PubMed  CAS  Google Scholar 

  • Felmeden DC, Blann AD, et al. (2003) Angiogenesis: Basic pathophysiology and implications for disease. Eur Heart J 24:585–603.

    Article  CAS  Google Scholar 

  • Ferrara N, Gerber HP, et al. (2003) The biology of VEGF and its receptors. Nat Med 9:669–676.

    Article  PubMed  CAS  Google Scholar 

  • Flanders KC, Lippa CF, et al. (1995) Altered expression of transforming growth factor-beta in Alzheimer’s disease. Neurology 45:561–569.

    Article  Google Scholar 

  • Forette F, Seux ML, et al. (1998) Prevention of dementia in randomized double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 352:1347–1351.

    Article  PubMed  CAS  Google Scholar 

  • Gimbrone MA, Jr., Topper JN, Nagel T, Anderson KR, Garcia-Cardena G (2000) Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann NY Acad Sci 902:239–240.

    Google Scholar 

  • Giunta B, Fernandez F, et al. (2008) Inflammaging as a prodrome to Alzheimer’s disease. J Neuroinflammation 5:51.

    Article  PubMed  CAS  Google Scholar 

  • Gorski DH, Leal AJ (2003) Inhibition of endothelial cell activation by the homeobox gene Gax. J Surg Res 111:91–99.

    Article  PubMed  CAS  Google Scholar 

  • Grammas P, Ovase R (2001) Inflammatory factors are elevated in brain microvessels in Alzheimer’s disease. Neurobiol Aging. 22:837–842.

    Article  PubMed  CAS  Google Scholar 

  • Grammas P, Ovase R (2002) Cerebrovascular TGF-β contributes to inflammation in the Alzheimer’s brain. Am J Pathol 160:1583–1587.

    Article  PubMed  CAS  Google Scholar 

  • Grammas P, Ottman T, et al. (2004) Injured endothelial cells release neurotoxic thrombin. J Alzheimers Dis 6:275–281.

    PubMed  CAS  Google Scholar 

  • Grammas P, Ghatreh-Samany P, et al. (2006) Thrombin and inflammatory proteins are elevated in Alzheimer’s disease microvessels: Implications for disease pathogenesis. J Alzheimers Dis 9:51–58.

    PubMed  CAS  Google Scholar 

  • Grilli M, Ferrari Toninelli G (2003) Alzheimer’s disease linking neurodegeneration with neurodevelopment. Funct Neurol 18:145–148.

    PubMed  Google Scholar 

  • Haralabopoulos GC, Grant DS, et al. (1997) Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo Am J Physiol 272:239–245.

    Google Scholar 

  • Haughey NJ, Mattson MP (2003) Alzheimer’s amyloid beta-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes. Neuromolecular Med 3:173–180.

    Article  PubMed  Google Scholar 

  • Heller R, Polack T, et al. (1999) Nitric oxide inhibits proliferation of human endothelial cells via a mechanism independent of cGMP. Atherosclerosis 144:49–57.

    Article  PubMed  CAS  Google Scholar 

  • Helzner EP, Luchsinger JA, et al. (2009) Contribution of vascular risk factors to the progression in Alzheimer’s disease. Arch Neurol 66:343–348.

    Article  PubMed  Google Scholar 

  • Hirohata M, Ono K, et al. (2008) Non-steroidal anti-inflammatory drugs as anti-amyloidogenic compounds. Curr Pharm Des 14:3280–3294.

    Article  PubMed  CAS  Google Scholar 

  • Huang Y-Q, LI J-J, et al. (2002) Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells. Blood 99:1646–1650.

    Article  PubMed  CAS  Google Scholar 

  • in t’ Veld BA, Ruitenberg A, et al. (2001) Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 345:1515–1521.

    Article  PubMed  Google Scholar 

  • Isenberg JS, Ridnour LA, et al. (2005) Thrombospondin-1 inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner. Proc Natl Acad Sci USA 102:13141–13146.

    Article  PubMed  CAS  Google Scholar 

  • Jellinger KA (2002) Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 109:813–836.

    Article  PubMed  CAS  Google Scholar 

  • Jones MK, Wang H, et al. (1999) Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med 5:1418–1423.

    Article  PubMed  CAS  Google Scholar 

  • Jones MK, Tsugawa K, et al. (2004) Dual actions of nitric oxide on angiogenesis: Possible roles of PKC, ERK and AP-1. Biochem Biophys Res Commun 318:520–528.

    Article  PubMed  CAS  Google Scholar 

  • Kalaria RN. Pax AB (1995) Increased collagen content of cerebral microvessels in Alzheimer’s disease. Brain Res 705:349–352.

    Article  PubMed  CAS  Google Scholar 

  • Kalaria RN, Cohen DL, et al. (1998) Vascular endothelial growth factor in Alzheimer’s disease and experimental ischemia. Brain Res Mol Brain Res 62:101–105.

    Article  PubMed  CAS  Google Scholar 

  • Karamysheva AF (2008) Mechanisms of angiogenesis. Biochemistry (Mosc) 73:751–762.

    Article  CAS  Google Scholar 

  • Kasuno K, Takabuchi S, et al. (2004) Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signaling. J Biol Chem 279:2550–2558.

    Article  PubMed  CAS  Google Scholar 

  • Kitaguchi H, Ihara M, et al. (2007) Tomimoto H. Capillary beds are decreased in Alzheimer’s disease, but not in Binswanger’s disease. Neurosci Lett 417:128–131.

    Article  PubMed  CAS  Google Scholar 

  • Kouznetsova E, Klinger M, et al. (2006) Developmental and amyloid plaque-related changes in cerebral cortical capillaries in transgenic mice Tg2576 Alzheimer mice. Int J Dev Neurosci 24:187–193.

    Article  PubMed  CAS  Google Scholar 

  • Kumar-Singh S (2009) Hereditary and sporadic forms of abeta-cerebrovascular amyloidosis and relevant transgenic mouse models. Int J Mol Sci 10:1872–1895.

    Article  PubMed  CAS  Google Scholar 

  • Lanari A, Silvestrelli G, et al. (2007) Arterial hypertension and cognitive dysfunction in physiologic and pathologic aging of the brain. Am J Geriatr Cardiol 16:158–164.

    Article  PubMed  Google Scholar 

  • Lathia JD, Mattson MP, et al. (2008) Notch: From neural development to neurological diseases. J Neurochem 107:1471–1481.

    Article  PubMed  CAS  Google Scholar 

  • Leung DW, Cachianes G, et al. (1989) Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 246:1306–1309.

    Article  PubMed  CAS  Google Scholar 

  • Lukiw WJ, Ottlecz A, et al. (2003) Coordinate activation of HIF-1 and NF-kappaB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia. Invest Ophthalmol Vis Sci 44:4163–4170.

    Article  PubMed  Google Scholar 

  • Li JL, Harris AL (2009) Crosstalk of VEGF and Notch pathways in tumor angiogenesis: Therapeutic implications. Front Biosci 14:3094–3110.

    Article  PubMed  CAS  Google Scholar 

  • Li M, Shang DS, et al. (2009) Amyloid beta interaction with receptor for advanced glycation end products up-regulates brain endothelial CCR5 expression and promotes T cells crossing the blood-brain barrier. J Immunol 182:5778–5788.

    Article  PubMed  CAS  Google Scholar 

  • Magrane J, Christensen RA, et al. (2006) Dissociation of ERK and Akt signaling in endothelial cell angiogenic responses to beta-amyloid. Exp Cell Res 312:996–1010.

    Article  PubMed  CAS  Google Scholar 

  • Maragoudakis ME, Tsopanoglou NE, et al. (2002) Mechanism of thrombin-induced angiogenesis. Biochem Soc Trans 30:173–177.

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, Klegeris A, et al. (1994) Pathological proteins in senile plaques. Tohoku J Exp Med 174:269–277.

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, Schulzer M, et al. (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: A review of 17 epidemiologic studies. Neurology 47:425–432.

    Article  PubMed  CAS  Google Scholar 

  • Menge T, Hartung HP, et al. (2005) Statins—a cure-all for the brain? Nat Rev Neurosci 6:325–331.

    Article  PubMed  CAS  Google Scholar 

  • Meyer EP, Ulmann-Schuler A, et al. (2008) Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer’s disease. Proc Natl Acad Sci USA. 105:3587–3592.

    Article  PubMed  CAS  Google Scholar 

  • Mhatre M, Nguyen A, et al. (2004) a mediator of neurotoxicity and memory impairment. Neurobiol Aging. 25:783–793.

    Article  PubMed  CAS  Google Scholar 

  • Miklossy J (2003) Cerebral hypoperfusion induces cortical watershed microinfarcts which may further aggravate cognitive decline in Alzheimer’s disease. Neurol Res 25:605–610.

    Article  PubMed  Google Scholar 

  • Milkiewicz M, Ispanovic E, et al. (2006) Regulators of angiogenesis and strategies for their therapeutic manipulation. Int J Biochem Cell Biol 38:333–357.

    Article  PubMed  CAS  Google Scholar 

  • Miller JW (1999) Homocysteine and Alzheimer’s disease. Nutr Rev 57:126–129.

    PubMed  CAS  Google Scholar 

  • Miyakawa T, Shimoji A, et al. (1982) The relationship between senile plaques and cerebral blood vessels in Alzheimer’s disease and senile dementia. Morphological mechanism of senile plaque production. Virchows Arch (Cell Pathol) 40:121–129.

    Article  CAS  Google Scholar 

  • Miyakawa T, Kimura T, et al. (2000) Role of blood vessels in producing pathological changes in the brain with Alzheimer’s disease. Ann NY Acad Sci. 903:46–54.

    Article  PubMed  CAS  Google Scholar 

  • Naldini A, Carney DH, et al. (2000) Thrombin regulates the expression of proangiogenic cytokines via proteolytic activation of protease-activated receptor-1 Gen Pharmacol 35:255–259.

    Article  PubMed  CAS  Google Scholar 

  • Nieves BJ, D’Amore PA, et al. (2009) The function of vascular endothelial growth factor. Biofactors 2009 [Epub ahead of print].

    Google Scholar 

  • Okada M, Suzuki K, et al. (2006) Detection of up-regulated genes in thrombin-stimulated human umbilical vein endothelial cells. Thromb Res 118:715–721.

    Article  PubMed  CAS  Google Scholar 

  • Pansari K, Gupta A, et al. (2002) Alzheimer’s disease and vascular factors: facts and theories. Int J Clin Pract 56:197–203.

    PubMed  CAS  Google Scholar 

  • Papapetropoulos A, Garcia-Cardena G, et al. (2005) Nitric Oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial. J Clin Invest 100:13141–13146.

    Google Scholar 

  • Paris D, Townsend KP, et al. (2002) Pro-inflammatory effort of freshly solubilized beta-amyloid peptides in the rain. Prostaglandins Other Lipid Mediat 70:1–12.

    Article  PubMed  CAS  Google Scholar 

  • Paris D, Patel N, et al. (2004a) Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis. Neurosci Lett 366:80–85.

    Article  PubMed  CAS  Google Scholar 

  • Paris D, Townsend K, et al. (2004b) Inhibition of angiogenesis by Aβ peptides. Angiogenesis 7:75–85.

    Article  PubMed  CAS  Google Scholar 

  • Paris D, Ait-Ghezala G, et al. (2005) Anti-angiogenic activity of the mutant Dutch Aβ peptide on human brain microvascular endothelial cells. Mol Brain Res 136:212–230.

    Article  PubMed  CAS  Google Scholar 

  • Park HJ, Kong D, et al. (2002) 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circ Res 91:143–150.

    Article  PubMed  CAS  Google Scholar 

  • Pasinetti GM (2002) From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer’s disease: The role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia. J Alzheimers Dis 4:435–445.

    PubMed  CAS  Google Scholar 

  • Patel NS, Quadros A, et al. (2008) Potent anti-angiogenic motifs within the Alzheimer beta amyloid peptide. Amyloid 15:5–19.

    Article  PubMed  CAS  Google Scholar 

  • Patel S, Leal AD, et al. (2005) The homeobox gene Gax inhibits angiogenesis through inhibition of nuclear factor-kappaB-dependent endothelial cell gene expression. Cancer Res 65:1414–1424.

    Article  PubMed  CAS  Google Scholar 

  • Pereira HA, Kumar P, et al. (1996) Expression of CAP37, a novel inflammatory mediator, in Alzheimer’s disease. Neurobiol Aging 17:753–759.

    Article  PubMed  CAS  Google Scholar 

  • Pogue AI, Lukiw WJ (2004) Angiogenic signaling in Alzheimer’s disease. Neuroreport 15:1507–1510.

    Article  PubMed  Google Scholar 

  • Previti ML, Zhang W, et al. (2006) Dexamethasone diminishes the pro-inflammatory and cytotoxic effects of amyloid beta-protein in cerebrovascular smooth muscle cells. J Neuroinflammation 3:18.

    Article  PubMed  CAS  Google Scholar 

  • Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9:677–684.

    Article  PubMed  CAS  Google Scholar 

  • Rao HV, Thirumangalakudi L, et al. (2007) Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons. J Neurochem 101:498–505.

    Article  PubMed  CAS  Google Scholar 

  • Rao HV, Thirumangalakudi L, et al. (2009) Cyclin C and cyclin dependent kinases 1,2 and 3 in thrombin-induced neuronal cell cycle progression and apoptosis. Neurosci Lett 450:347–350.

    Article  PubMed  CAS  Google Scholar 

  • Ridker PM, Silvertown JD (2008) Inflammation, C-reactive protein, and atherothrombosis. J Periodontol. 79:1544–1551.

    Article  PubMed  CAS  Google Scholar 

  • Rogers J (2008) The inflammatory response in Alzheimer’s disease. J Periodontol 79:1535–1543.

    Article  PubMed  CAS  Google Scholar 

  • Rosendorff C, Beeri MS, et al. (2007) Cardiovascular risk factors for Alzheimer’s disease. Am J Geriatr Cardiol 16:143–149.

    Article  PubMed  Google Scholar 

  • Ruiz de Almodovar C, Lambrechts D, et al. (2009) Role and therapeutic potential of VEGF in the nervous system. Physiol Rev. 89:607–648.

    Article  CAS  Google Scholar 

  • Ryu JK, McLarnon JG (2008) Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer’s disease brain. Neurobiol Dis 29:254–266.

    Article  PubMed  CAS  Google Scholar 

  • Scheibel AB (1984) Changes in brain capillary structure in aging and dementia: In J Wertheimer and M Marois, (Eds.) Senile Dementia Outlook for the Future Alan R. Liss, New York; NY pp. 137–149.

    Google Scholar 

  • Schmidt R, Schmidt H, et al. (2000) Vascular risk factors in dementia. J Neurol 247:81–87.

    Article  PubMed  CAS  Google Scholar 

  • Shi J, Perry G, et al. (2000) Vascular abnormalties: the insidious pathogenesis of Alzheimer’s disease. Neurobiol Aging 21:357–361.

    Article  PubMed  CAS  Google Scholar 

  • Siekmann AF, Lawson ND (2007) Notch signaling and the regulation of angiogenesis. Cell Adh Migr 1:104–106.

    Article  PubMed  Google Scholar 

  • Soffer D (2006) Cerebral amyloid angiopathy—a disease or age-related condition. Isr Med Assoc 8:803–806.

    CAS  Google Scholar 

  • Sparks DL, Hunsaker JC, et al. (1990) Cortical senile plaques in coronary artery disease, aging and Alzheimer’s disease. Neurobiol Aging 11:601–607.

    Article  PubMed  CAS  Google Scholar 

  • Sparks DL, Liu H, et al. (1993) Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals. J Neuropath Exp Neurol 52:135–142.

    Article  PubMed  CAS  Google Scholar 

  • Stampfer MJ (2006) Cardiovascular disease and Alzheimer’s disease: Common links. J Intern Med 260:211–223.

    Article  PubMed  CAS  Google Scholar 

  • Stern DM, Bank I Nawroth PP, et al. (1985) Self-regulation of procoagulant events on the endothelial cell surface. J Exp Med 162:1223–1229.

    Article  PubMed  CAS  Google Scholar 

  • Stewart R, Prince M, et al. (1999) Vascular risk factors and Alzheimer’s disease. Aust N Z Psychiatry 33:809–813.

    Article  CAS  Google Scholar 

  • Storkebaum E, Lambrechts D, et al. (2004) VEGF: Once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays 26:943–954.

    Article  PubMed  CAS  Google Scholar 

  • Stüve O, Youssef S, et al. (2003) Statins as potential therapeutic agents in neuroinflammatory disorders. Curr Opin Neurol 16:393–401.

    Article  PubMed  Google Scholar 

  • Suo Z, Tan J, et al. (1998) Alzheimer’s beta-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40. Brain Res. 807:110–117.

    Article  PubMed  CAS  Google Scholar 

  • Suo Z, Wu M, et al. (2003) Rapid tau aggregation and delayed hippocampal neuronal death induced by persistent thrombin signaling. J Biol Chem 278:37681–37689.

    Article  PubMed  CAS  Google Scholar 

  • Tarkowski E, Issa R, et al. (2002) Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer’s disease and vascular dementia. Neurobiol Aging 23:237–243.

    Article  PubMed  CAS  Google Scholar 

  • Tarnawski AS, Jones MK (2003) Inhibition of angiogenesis by NSAIDs: Molecular mechanisms and clinical implications. J Mol Med 81:627–636.

    Article  PubMed  CAS  Google Scholar 

  • Thirumangakudi L, Ghatreh-Samany P, et al. (2006) Angiogenic proteins are expressed by brain blood vessels in Alzheimer’s disease. J Alzeimers Dis. 10:111–118.

    Google Scholar 

  • Tian J, Shi J, et al. (2004) Cerebral amyloid angiopathy and dementia. Panminerva Med 46:253–264.

    PubMed  CAS  Google Scholar 

  • Tsopanoglou NE, Maragoudakis ME (1999) On the mechanism of thrombin-induced angiogenesis. Potentiation of vascular endothelial growth factor activity on endothelial cells by regulation of its receptors. J Biol Chem 274:23969–23976.

    Article  PubMed  CAS  Google Scholar 

  • Tsopanoglou NE, Andriopoulou P, et al. (2002) On the mechanism of thrombin-induced angiogenesis: Involvement of alphavbeta3-integrin. Am J Physiol 283:C1501–C1510.

    CAS  Google Scholar 

  • Turgeon VL, Milligan CE, et al. (1999) Activation of the protease-activated thrombin receptor (PAR)-1 induces motoneuron degeneration in the developing avian embryo. J Neuropathol Exp Neurol 58:499–504.

    Article  PubMed  CAS  Google Scholar 

  • Van Guldener C, Stehouwer CD (2000) Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Semin Thromb Hemost 26:281–289.

    Article  PubMed  Google Scholar 

  • Verheul HM, Jorna AS, et al. (2000) Pinedo HM. Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets. Blood 96:4216–4221.

    PubMed  CAS  Google Scholar 

  • Vukic V, Callaghan D, et al. (2009) Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial cells and in Alzheimer’s brain is mediated by the JNK-AP1 signaling pathway. Neurobiol Dis 34:95–106.

    Article  PubMed  CAS  Google Scholar 

  • Walker DG, Dalsing-Hernandez JE, et al. (2008) Human post-mortem brain-derived cerebrovascular smooth muscle cells express all genes of the classical complement pathway: A potential mechanism for vascular damage in cerebral amyloid angiopathy and Alzheimer’s disease. Microvasc Res 75:411–419.

    Article  PubMed  CAS  Google Scholar 

  • Warrington K, Hillarby MC, et al. (2005) Functional role of CD105 in TGF-beta1 signalling in murine and human endothelial cells. Anticancer Res 25:1851–1864.

    PubMed  CAS  Google Scholar 

  • Weggen S, Rogers M, et al. (2007) NSAIDs: Small molecules for prevention of Alzheimer’s disease or precursors for future drug development? Trends Pharmacol Sci 28:536–543.

    Article  PubMed  CAS  Google Scholar 

  • Weller RO, Boche D, et al. (2009) Microvasculature changes and cerebral amyloid angiopathy in Alzheimer’s disease and their potential impact on therapy. Acta Neuropathol 118:87–102.

    Article  PubMed  CAS  Google Scholar 

  • Wilcock DM, Vitek MP, et al. (2009) Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer’s disease. Neuroscience 159:1055–1069.

    Article  PubMed  CAS  Google Scholar 

  • Williams S, Chalmers K, et al. (2005) Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer’s disease. Neuropathol Appl Neurobiol 31:414–421.

    Article  PubMed  CAS  Google Scholar 

  • Wolozin B, Kellman W, et al. (2000) Decreased prevalence of Alzheimer’s disease associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arch Neurol 57:1439–1443.

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Ma J, et al. (2006) Distinct regulation of gene expression in human endothelial cells by TGF-beta and its receptors. Microvasc Res 71:12–19.

    Article  PubMed  CAS  Google Scholar 

  • Wu Z, Guo H, et al. (2005) Role of the MEOX2 gene in neurovascular dysfunction in Alzheimer disease. Nat Med 11:959–956.

    Google Scholar 

  • Yagami T (2006) Cerebral arachidonate cascade in dementia: Alzheimer’s disease and vascular dementia. Curr Neuropharmacol 4:87–100.

    Article  PubMed  CAS  Google Scholar 

  • Yamakawa M, Liu LX, et al. (2003) Hypoxia-inducible factor-1 mediates activation of cultured vascular endothelial cells by inducing multiple angiogenic factors. Circ Res 93:664–673.

    Article  PubMed  CAS  Google Scholar 

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  1. Garrison Institute on Aging, and Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Paula Grammas

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  1. Paula Grammas
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Correspondence to Paula Grammas .

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  1. , SBCHS, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, United Kingdom

    Mark Slevin

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Grammas, P. (2010). Angiogenic Mediators and the Pathogenesis of Alzheimer’s Disease. In: Slevin, M. (eds) Therapeutic Angiogenesis for Vascular Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9495-7_13

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