A new paradigm for the treatment of alzheimer's disease: Targeting vascular activation

Journal of Alzheimer's Disease

Volumn 40, Issue 3, 2014, Pages 619-630

  Grammas, Paula ^a,b   Martinez, Joseph ^a   Sanchez, Alma ^a   Yin, Xiangling ^a   Riley, Jarred ^a   Gay, Dylan ^a   Desobry, Katherine ^a   Tripathy, Debjani ^a   Luo, Jinhua ^a   Evola, Marianne ^b   Young, Alice ^b  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b TEXAS TECH UNIVERSITY   (United States)

Author keywords

Alzheimer's disease; angiogenesis; behavior; cognitive decline; sunitinib

Indexed keywords

AMYLOID BETA PROTEIN; GELATINASE B; INTERLEUKIN 1BETA; INTERLEUKIN 6; SUNITINIB; THROMBIN; TUMOR NECROSIS FACTOR ALPHA; AMYLOID PRECURSOR PROTEIN; ANGIOGENESIS INHIBITOR; ANTIFIBRINOLYTIC AGENT; INDOLE DERIVATIVE; MENADIONE; PRESENILIN 1; PSEN1 PROTEIN, HUMAN; PYRROLE DERIVATIVE;

ALZHEIMER DISEASE; ANGIOGENESIS; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN CELL; BRAIN TISSUE; CARDIOVASCULAR RISK; COGNITION; CONTROLLED STUDY; DRUG EFFECT; ENDOTHELIUM CELL; MOUSE; NEUROPATHOLOGY; NONHUMAN; OPEN FIELD TEST; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; AVOIDANCE BEHAVIOR; BLOOD VESSEL; BRAIN; C57BL MOUSE; DRUG EFFECTS; GENETICS; HUMAN; MALE; MOTOR ACTIVITY; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; REACTION TIME; TIME; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANGIOGENESIS INHIBITORS; ANIMALS; ANTIFIBRINOLYTIC AGENTS; AVOIDANCE LEARNING; BLOOD VESSELS; BRAIN; ENDOTHELIAL CELLS; HUMANS; INDOLES; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MOTOR ACTIVITY; PRESENILIN-1; PYRROLES; REACTION TIME; TIME FACTORS; VITAMIN K 3;

EID: 84901918946     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-2014-132057     Document Type: Article

References (73)

1. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9, 63-75.
2. Alzheimer's, Association (2013) 2013 Alzheimer's disease facts and figures. Alzheimers Dement 9, 208-245.
3. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356. (Pubitemid 34790756)
4. Pimplikar SW (2009) Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int J Biochem Cell Biol 41, 1261-1268.
5. Aisen PS, Andrieu S, Sampaio C, Carrillo M, Khachaturian ZS, Dubois B, Feldman HH, Petersen RC, Siemers E, Doody RS, Hendrix SB, Grundman M, Schneider LS, Schindler RJ, Salmon E, Potter WZ, Thomas RG, Salmon D, Donohue M, Bednar MM, Touchon J, Vellas B (2011) Report of the task force on designing clinical trials in early (predementia) AD. Neurology 76, 280-286.
6. Castellani RJ, Perry G (2012) Pathogenesis and diseasemodifying therapy in Alzheimer's disease: The flat line of progress. Arch Med Res 43, 694-698.
7. Frautschy SA, ColeGM(2010)Whypleiotropic interventions are needed for Alzheimer's disease. Mol Neurobiol 41, 392- 409.
8. Green RC, Schneider LS, Amato DA, Beelen AP, Wilcock G, Swabb EA, Zavitz KH; Tarenflurbil Phase 3 Study Group (2009) Effect of tarenfluribil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 302, 2557-2564.
9. Tolppanen AM, Solomon A, Soininen H, KivipeltoM(2012) Midlife vascular risk factors and Alzheimer's disease: evidence from epidemiological studies. J Alzheimers Dis 32, 531-540.
10. Justin BN, Turek M, Hakim AM (2013) Heart disease as a risk factor for dementia. Clin Epidemiol 5, 135-145.
11. Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM, Stern Y (2009) Contribution of vascular risk factors to the progression in Alzheimer's disease. Arch Neurol 66, 343-348.
12. Dickstein DL,Walsh J, Brautigam H, Stockton SD Jr, Gandy S, Hof PR (2010) Role of vascular risk factors and vascular dysfunction in Alzheimer's disease. Mt Sinai J Med 77, 82- 102.
13. Shah NS, Vidal JS, Masaki K, Petrovitch H, Ross GW, Tilley C, DeMattos RB, Tracy RP, White LR, Launer LJ (2012) Midlife blood pressure, plasma -amyloid, and risk for Alzheimer disease: the Honolulu Asia Aging Study. Hypertension 59, 780-786.
14. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, BretelerMM(1999) Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 53, 1937-1942.
15. Janson J, Laedtke T, Parisi JE, O'Brien P, Petersen RC, Butler PC (2004) Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53, 474-481. (Pubitemid 38174565)
16. Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, van Harskamp F, van Duijn CN, Van Broeckhoven C, Grobbee DE (1997) Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 349, 151-154. (Pubitemid 27039193)
17. Grammas P (2011) Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer's disease. J Neuroinflammation 8, 26.
18. Grammas P,OvaseR(2001) Inflammatory factors are elevated in brain microvessels in Alzheimer's disease. Neurobiol Aging 22, 837-842. (Pubitemid 34066550)
19. Grammas P, Ovase R (2002) Cerebrovascular TGF- contributes to inflammation in the Alzheimer's brain. Am J Pathol 160, 1583-1587. (Pubitemid 34525638)
20. Thirumangalakudi L, Samany PG, Owoso A, Wiskar B, Grammas P (2006) Angiogenic proteins are expressed by brain blood vessels in Alzheimer's disease. J Alzheimers Dis 10, 111-118. (Pubitemid 44401371)
21. Yin X,Wright J,Wall T, Grammas P (2010) Brain endothelial cells synthesize neurotoxic thrombin in Alzheimer's disease. Am J Pathol 176, 1600-1606.
22. Rini BI (2007) Sunitinib. Expert Opin Pharmacolther 8, 2359- 2369. (Pubitemid 350001595)
23. Shibuya M (2013) Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem 153, 13-19.
24. Schweighofer B, Testori J, Sturtzel C, Sattler S, Mayer H, Wagner O, Bilban M, Hofer E (2009) The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation. ThrombHaemost 102, 544-554.
25. Patyna S, Peng J (2006) Distribution of sunitinib and its active metabolite in brain and spinal cord tissue following oral or intravenous administration in rodents and monkeys. Eur J Cancer 4, 21.
26. Blaney CE, Gunn RK, Stover KR, Brown RE (2013) Maternal genotype influences behavioral development of 3xTg-AD mouse pups. Behav Brain Res 252, 40-48.
27. Morgan D, Munireddy S, Alamed J, DeLeon J, Diamond DM, Bickford P, Hutton M, Lewis J, McGowan E, Gordon MN (2008) Apparent behavioral benefits of tau overexpression in P301L tau transgenic mice. J Alzheimers Dis 15, 605-614.
28. MorrisRGM(1984) Development of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11, 47-60.
29. Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM (2005) Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 45, 675-688. (Pubitemid 40320703)
30. Evola M, Hall A,Wall T,Young A, Grammas P (2010) Oxidative stress impairs learning and memory in apoE knockout mice. Pharmacol Biochem Behav 96, 181-186.
31. Diglio CA, LiuW, Grammas P, Giacomelli F,Wiener J (1993) Isolation and characterization of cerebral resistance vessel endothelium in culture. Tissue Cell 25, 833-846. (Pubitemid 24025814)
32. TripathyD, Sanchez A,YinX, Martinez J, Grammas P (2012) Age-related decrease in cerebrovascular-derived neuroprotective proteins: effect of acetaminophen. Microvasc Res 84, 278-285.
33. Sterniczuk R, Antel MC, LaFerla FM, Dyck RH (2010) Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 2. Behavioral and cognitive changes. Brain Res 1348, 149-155.
34. Warren MC, Bump EA, Medeiros D, Braunhut SJ (2000) Oxidative stress-induced apoptosis of endothelial cells. Free Radic Biol Med 29, 537-547.
35. de la Torre JC (2004) Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 3, 184-190. (Pubitemid 38232669)
36. Bell RD, Zlokovic BV (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol 118, 103-113.
37. Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, HoltzmanDM,Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV (2012) Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485, 512-516.
38. Zlokovic BV (2013) Cerebrovascular effects of apolipoprotein E: implications for Alzheimer's disease. JAMA Neurol 70, 440-444.
39. Meyer EP, Ulmann-Schuler A, Staufenbiel M, Krucker T (2008) Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease. Proc Natl Acad Sci U S A 105, 3587-3592. (Pubitemid 351723596)
40. Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci 28, 202- 208. (Pubitemid 40445527)
41. Yu D, Corbett B, Yan Y, Zhang GX, Reinhart P, Cho SJ, Chin J (2012) Early cerebrovascular inflammation in a transgenic mouse model of Alzheimer's disease. Neurobiol Aging 33, 2942-2947.
42. Vlad SC, Miller DR, Kowall NW, Feson DT (2008) Protective effects of NSAIDs on the development of Alzheimer's disease. Neurology 70, 1672-1677. (Pubitemid 351644133)
43. Lim GP (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 20, 5709-5714. (Pubitemid 30636898)
44. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ; Alzheimer's Disease Cooperative Study (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized clinical trial. JAMA 289, 2819- 2826. (Pubitemid 37430117)
45. ADAPT Research Group, Martin BK, Szekely C, Brandt J, Piantadosi S, Breitner JC, Craft S, Evans D, Green R, Mullan M(2008) Cognitive function over time in the Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 65, 896-905. (Pubitemid 352008472)
46. Gimbrone MA Jr, Garc'ia-Carde?na G (2013) Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovasc Pathol 22, 9-15.
47. Miklossy J (2003) Cerebral hypoperfusion induces cortical watershed microinfarcts which may further aggravate cognitive decline in Alzheimer's disease. Neurol Res 25, 605-610. (Pubitemid 37087604)
48. Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9, 677-684. (Pubitemid 36749216)
49. Grammas P, Samany PG, Thirumangalakudi L (2006) Thrombin and inflammatory proteins are elevated in Alzheimer's disease microvessels: implications for disease pathogenesis. J Alzheimers Dis 9, 51-58.
50. Tripathy D, Sanchez A, Yin X, Luo J, Martinez J, Grammas P (2013) Thrombin, a mediator of cerebrovascular inflammation in AD and hypoxia. Front Aging Neurosci 5, 19.
51. Bu'ee L, Hof PR, Bouras C, Delacourte A, Perl DP, Morrison JH, Fillit HM (1994) Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders. Acta Neuropathol 87, 469-480. (Pubitemid 24128974)
52. Bu'ee L, Hof PR, Delacourte A (1997) Brain microvascular changes in Alzheimer's disease and other dementias. Ann NY Acad Sci 826, 7-24. (Pubitemid 27478027)
53. Jellinger KA (2002) Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 109, 813-836. (Pubitemid 34810776)
54. Paris D, Patel N, DelleDonne A, Quadros A, Smeed R, Mullan M(2004) Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis. Neurosci Lett 366, 80-85. (Pubitemid 38953153)
55. Paris D, Townsend K, Quadros A, Humphrey J, Sun J, Brem S,Wotoczek-Obadia M, DelleDonne A, Patel N, Obregon DF, Crescentini R, Abdullah L, Coppola D, RojianiAM,Crawford F, Sebti SM, Mullan M (2004) Inhibition of angiogenesis by A peptides. Angiogenesis 7, 75-85.
56. Deane R, Bell RD, Sagare A, Zlokovic BV (2009) Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol Disord Drug Targets 8, 16-30.
57. Ciallela JR, Figueiredo H, Smith-Swintosky V, McGillis JP (1999) Thrombin induces surface and intracellular secretion of amyloid precursor protein from human endothelial cells. Thromb Haemost 81, 630-637. (Pubitemid 29178954)
58. Muche A, B?rger S, Arendt T, Schliebs R (2013) Hypoxic stress, brain vascular system, and -amyloid: A primary cell culture study. Nutr Neurosci, doi: 10.1179/1476830513Z. 000000000112
59. Rajadas J, SunW, Li H, Inayathullah M, Cereghetti D, Tan A, de Mello Coelho V, Chrest FJ, Kusiak JW, Smith WW, Taub D,Wu JC, Rifkind JM (2013) EnhancedA(1-40) production in endothelial cells stimulated with fibrillar A(1-42). PLoS One 8, e58194.
60. Li M, Shang DS, Zhao WD, Tian L, Li B, Fang WG, Zhu L, Man SM, Chen YH (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.
61. Vukic V, Callaghan D, Walker D, Lue LF, Liu QY, Couraud PO, Romero IA, Weksler B, Stanimirovic DB, Zhang W (2009) Expression of inflammatory genes induced by betaamyloid peptides in human brain endothelial cells and in Alzheimer's brain is mediated by the JNK-AP1 signaling pathway. Neurobiol Dis 34, 95-106.
62. Paris D, Townsend KP, Obregon DF, Humphrey J, Mullan M (2002) Pro-inflammatory effort of freshly solubilized betaamyloid peptides in the brain. Prostaglandins Other Lipid Mediat 70, 1-12.
63. Akiyama H, Ikeda K, Kondo H, McGeer PL (1992) Thrombin accumulation in patients with Alzheimer's disease. Neurosci Lett 146, 152-154.
64. Zipser BD, Johanson CE, Gonzalez L, Berzin TM, Tavares R, Hulette CM, Vitek MP, Hovanesian V, Stopa EG (2007) Microvascular injury and blood-brain barrier leakage in Alzheimer's disease. Neurobiol Aging 28, 977-986. (Pubitemid 46635913)
65. Gim'enez-Llort L, Bl'azquez G, Canete T, Johansson B, Oddo S, Tobena A, LaFerla FM, Fern'andez-TeruelA(2007) Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: A role for intraneuronal amyloid. Neurosci Biobehav Rev 31, 125-147. (Pubitemid 44895427)
66. Medeiros R, Prediger RD, Passos GF, Pandolfo P, Duarte FS, Franco JL, Dafre AL, Di Giunta G, Fiqueiredo CP, Takahashi RN, Campos MM, Calixto JB (2007) Connecting TNF-alpha signaling pathways to iNOS expression in a mouse model of Alzheimer's disease: relevance for the behavioral and synaptic deficits induced by amyloid protein. J Neurosci 27, 5394- 5404. (Pubitemid 46790177)
67. Xu WJ, Xu F, Anderson ME, Kotarba AE, Davis J, Robinson JK, Van Nostrand WE (2013) Cerebral microvascular rather than parenchymal amyloid -protein pathology promotes early cognitive impairment in transgenic mice. J Alzheimers Dis 38, 621-632.
68. Sanchez A, Tripathy D, Yin X, Luo J, Martinez JM, Grammas P (2013) Sunitinib enhances neuronal survival in vitro via NF- κB-mediated signaling and expression of cyclooxygenase-2 and inducible nitric oxide synthase. J Neuroinflammation 10, 93.
69. Schwartz E, Wicinski B, Schmeidler J, Haroutunian V, Hof PR (2010) Cardiovascular risk factors affect hippocampal microvasculature in early AD. Transl Neurosci 1, 292-299.
70. Deschaintre Y, Richard F, Leys D, Pasquier F (2009) Treatment of vascular risk factors is associated with slower decline in Alzheimer disease. Neurology 73, 674-680.
71. Akinyemi RO, Mukaetova-Ladinska EB, Attems J, Ihara M, Kalaria RN (2013) Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer's disease and vascular dementia. Curr Alzheimer Res 10, 642-653.
72. Owens CD (2012) Statins and other agents for vascular inflammation. J Vasc Surg 56, 1799-1806.
73. Corrao F, Ibrahim B, Nicotra F, Zambon A, Merlino L, Pasini TS, Catapano AL, Mancia G (2013) Long-term use of statins reduces the risk of hospitalization for dementia. Atherosclerosis 230, 171-176.