The role of iron-induced fibrin in the pathogenesis of Alzheimer's disease and the protective role of magnesium

Frontiers in Human Neuroscience

Volumn , Issue OCT, 2013, Pages

  Lipinski, Boguslaw ^a   Pretorius, Etheresia ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF PRETORIA   (South Africa)

Author keywords

Alzheimer's disease; Fibrin; Iron; Magnesium; Red blood cells

Indexed keywords

ALBUMIN; ALIPHATIC COMPOUND; AMYLOID BETA PROTEIN; CHLOROPHYLL; EPIGALLOCATECHIN GALLATE; FERULIC ACID; FIBRIN; FIBRINOGEN; HYDROXYL RADICAL; IRON; MAGNESIUM; MAGNESIUM CHLORIDE; MAGNESIUM SULFATE; NORPHENAZONE; OMEGA 3 FATTY ACID; POLYPHENOL DERIVATIVE; POLYUNSATURATED FATTY ACID; REACTIVE OXYGEN METABOLITE; RESVERATROL;

ALZHEIMER DISEASE; ANTICOAGULATION; ARTICLE; BLOOD CLOT; BRAIN HYPOXIA; BRAIN INFARCTION; CARDIOVASCULAR DISEASE; CHRONIC INFLAMMATION; DEGENERATIVE DISEASE; DIABETIC NEUROPATHY; DIET RESTRICTION; ECLAMPSIA; ERYTHROCYTE AGGREGATION; FENTON REACTION; FIBRIN CLOT; FIBRIN DEPOSITION; FIBRINOLYSIS; HEMOSTASIS; HUMAN; HYPOMAGNESEMIA; MAGNESIUM DEFICIENCY; MEDITERRANEAN DIET; NEUROPROTECTION; OCCLUSIVE CEREBROVASCULAR DISEASE; OXIDATIVE STRESS; PATHOGENESIS; PREECLAMPSIA; PROTEIN AGGREGATION; PROTEIN DEGRADATION; RED MEAT; VASCULAR AMYLOIDOSIS;

EID: 84887884236     PISSN: 16625161     EISSN: None     Source Type: Journal    
DOI: 10.3389/fnhum.2013.00735     Document Type: Article

References (192)

1. Abe, S., Kirima, K., Tsuchiya, K., Okamoto, M., Hasegawa, T., Houchi, H., et al. (2004). The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) with hydroxyl radical. Chem. Pharm. Bull. 52, 186-191. doi: 10. 1248/cpb. 52. 186.
2. Adamopoulos, C., Pitt, B., Sui, X., Love, T. E., Zannad, F., and Ahmed, A. (2009). Low serum magnesium and cardiovascular mortality in chronic heart failure: a propensity-matched study. Int. J. Cardiol. 136, 270-277. doi: 10. 1016/j. ijcard. 2008. 05. 006.
3. Adeghate, E., Donath, T., and Adem, A. (2013). Alzheimer disease and diabetes mellitus: do they have anything in common? Curr. Alzheimer Res. 10, 609-617. doi: 10. 2174/15672050113109990009.
4. Adlard, P. A., and Bush, A. I. (2006). Metals and Alzheimer's disease. J. Alzheimers Dis. 10, 145-163.
5. Ahluwalia, N., Genoux, A., Ferrieres, J., Perret, B., Carayol, M., Drouet, L., et al. (2010). Iron status is associated with carotid atherosclerotic plaques in middle-aged adults. J. Nutr. 140, 812-816. doi: 10. 3945/jn. 109. 110353.
6. Ahn, H. J., Zamolodchikov, D., Cortes-Canteli, M., Norris, E. H., Glickman, J. F., and Strickland, S. (2010). Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization. Proc. Natl. Acad. Sci. U. S. A. 107, 21812-21817. doi: 10. 1073/pnas. 1010373107.
7. Albrecht, E., Kirkham, K. R., Liu, S. S., and Brull, R. (2013). Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis. Anaesthesia 68, 79-90. doi: 10. 1111/j. 1365-2044. 2012. 07335. x.
8. Altamura, S., and Muckenthaler, M. U. (2009). Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J. Alzheimers Dis. 16, 879-895. doi: 10. 3233/JAD-2009-1010.
9. Ames, W. A., Mcdonnell, N., and Potter, D. (1999). The effect of ionised magnesium on coagulation using thromboelastography. Anaesthesia 54, 999-1001. doi: 10. 1046/j. 1365-2044. 1999. 00647. x.
10. Amighi, J., Sabeti, S., Schlager, O., Mlekusch, W., Exner, M., Lalouschek, W., et al. (2004). Low serum magnesium predicts neurological events in patients with advanced atherosclerosis. Stroke 35, 22-27. doi: 10. 1161/01. STR. 0000105928. 95124. 1F.
11. Andresdottir, M. B., Sigfusson, N., Sigvaldason, H., and Gudnason, V. (2003). Erythrocyte sedimentation rate, an independent predictor of coronary heart disease in men and women: the Reykjavik Study. Am. J. Epidemiol. 158, 844-851. doi: 10. 1093/aje/kwg222.
12. Angeloni, C., Pirola, L., Vauzour, D., and Maraldi, T. (2012). Dietary polyphenols and their effects on cell biochemistry and pathophysiology. Oxid. Med. Cell. Longev. 2012, 583901. doi: 10. 1155/2012/583901.
13. Assadi, F. (2010). Hypomagnesemia: an evidence-based approach to clinical cases. Iran J. Kidney Dis. 4, 13-19.
14. Ayissi, V. B., Ebrahimi, A., and Schluesenner, H. (2013). Epigenetic effects of natural polyphenols: a focus on SIRT1-mediated mechanisms. Mol. Nutr. Food Res. doi: 10. 1002/mnfr. 201300195.
15. Barbagallo, M., Belvedere, M., Di Bella, G., and Dominguez, L. J. (2011). Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease. Magnes. Res. 24, S115-S121. doi: 10. 1684/mrh. 2011. 0287.
16. Barnham, K. J., and Bush, A. I. (2008). Metals in Alzheimer's and Parkinson's diseases. Curr. Opin. Chem. Biol. 12, 222-228. doi: 10. 1016/j. cbpa. 2008. 02. 019.
17. Barr, J. D., Chauhan, A. K., Schaeffer, G. V., Hansen, J. K., and Motto, D. G. (2013). Red blood cells mediate the onset of thrombosis in the ferric chloride murine model. Blood121, 3733-3741. doi: 10. 1182/blood-2012-11-468983.
18. Baskurt, O. K., Yalcin, O., and Meiselman, H. J. (2004). Hemorheology and vascular control mechanisms. Clin. Hemorheol. Microcirc. 30, 169-178.
19. Baum, L., and Ng, A. (2004). Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J. Alzheimers Dis. 6, 367-377; discussion 443-369.
20. Beard, J. L., and Connor, J. R. (2003). Iron status and neural functioning. Annu. Rev. Nutr. 23, 41-58. doi: 10. 1146/annurev. nutr. 23. 020102. 075739.
21. Benarroch, E. E. (2009). Brain iron homeostasis and neurodegenerative disease. Neurology 72, 1436-1440. doi: 10. 1212/WNL. 0b013e3181a26b30.
22. Berk, M., Dean, O., Drexhage, H., Mcneil, J. J., Moylan, S., Oneil, A., et al. (2013). Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness. BMC Med. 11: 74. doi: 10. 1186/1741-7015-11-74.
23. Biernacki, E. (1897). Samoistna sedymentacja krwi, jako naukowa i praktyczno-kliniczna metoda badania (spontaneous sedimentation of red blood cells in clinical practice). Gazeta Lekarska 17, 962-964.
24. Bieschke, J., Russ, J., Friedrich, R. P., Ehrnhoefer, D. E., Wobst, H., Neugebauer, K., et al. (2010). EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proc. Natl. Acad. Sci. U. S. A. 107, 7710-7715. doi: 10. 1073/pnas. 0910723107.
25. Breuer, W., Shvartsman, M., and Cabantchik, Z. I. (2008). Intracellular labile iron. Int. J. Biochem. Cell Biol. 40, 350-354. doi: 10. 1016/j. biocel. 2007. 03. 010.
26. Brewer, G. J. (2007). Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease. Exp. Biol. Med. (Maywood) 232, 323-335.
27. Casadesus, G., Smith, M. A., Zhu, X., Aliev, G., Cash, A. D., Honda, K., et al. (2004). Alzheimer disease: evidence for a central pathogenic role of iron-mediated reactive oxygen species. J. Alzheimers Dis. 6, 165-169.
28. Castellani, R. J., Moreira, P. I., Perry, G., and Zhu, X. (2012). The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors 38, 133-138. doi: 10. 1002/biof. 1010.
29. Ceremuzynski, L., Gebalska, J., Wolk, R., and Makowska, E. (2000). Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J. Intern. Med. 247, 78-86. doi: 10. 1046/j. 1365-2796. 2000. 00585. x.
30. Chakrabarti, S., Sinha, M., Thakurta, I. G., Banerjee, P., and Chattopadhyay, M. (2013). Oxidative stress and amyloid beta toxicity in Alzheimer's disease: intervention in a complex relationship by antioxidants. Curr. Med. Chem.
31. Cheeseman, K. H., Beavis, A., and Esterbauer, H. (1988). Hydroxyl-radical-induced iron-catalysed degradation of 2-deoxyribose. Quantitative determination of malondialdehyde. Biochem. J. 252, 649-653.
32. Chetelat, G. (2013). Alzheimer disease: Abeta-independent processes-rethinking preclinical AD. Nat. Rev. Neurol. 9, 123-124. doi: 10. 1038/nrneurol. 2013. 21.
33. Choi, J., Malakowsky, C. A., Talent, J. M., Conrad, C. C., and Gracy, R. W. (2002). Identification of oxidized plasma proteins in Alzheimer's disease. Biochem. Biophys. Res. Commun. 293, 1566-1570. doi: 10. 1016/S0006-291X(02)00420-5.
34. Cilliler, A. E., Ozturk, S., and Ozbakir, S. (2007). Serum magnesium level and clinical deterioration in Alzheimer's disease. Gerontology 53, 419-422. doi: 10. 1159/000110873.
35. Ciriolo, M. R., De Martino, A., Lafavia, E., Rossi, L., Carri, M. T., and Rotilio, G. (2000). Cu, Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells. J. Biol. Chem. 275, 5065-5072. doi: 10. 1074/jbc. 275. 7. 5065.
36. Corica, F., Corsonello, A., Ientile, R., Cucinotta, D., Di Benedetto, A., Perticone, F., et al. (2006). Serum ionized magnesium levels in relation to metabolic syndrome in type 2 diabetic patients. J. Am. Coll. Nutr. 25, 210-215. doi: 10. 1080/07315724. 2006. 10719534.
37. Corrigan, F. M., Van Rhijn, A., and Horrobin, D. F. (1991). Essential fatty acids in Alzheimer's disease. Ann. N. Y. Acad. Sci. 640, 250-252.
38. Cortes-Canteli, M., Paul, J., Norris, E. H., Bronstein, R., Ahn, H. J., Zamolodchikov, D., et al. (2010). Fibrinogen and beta-amyloid association alters thrombosis and fibrinolysis: a possible contributing factor to Alzheimer's disease. Neuron 66, 695-709. doi: 10. 1016/j. neuron. 2010. 05. 014.
39. Craft, S. (2012). Alzheimer disease: insulin resistance and AD-extending the translational path. Nat. Rev. Neurol. 8, 360-362. doi: 10. 1038/nrneurol. 2012. 112.
40. Czapski, G. (1984). Reaction of OH. Meth. Enzymol. 105, 209-215. doi: 10. 1016/S0076-6879(84)05027-8.
41. Dajas-Bailador, F. A., Martinez-Borges, A., Costa, G., Abin, J. A., Martignoni, E., Nappi, G., et al. (1998). Hydroxyl radical production in the substantia nigra after 6-hydroxydopamine and hypoxia-reoxygenation. Brain Res. 813, 18-25. doi: 10. 1016/S0006-8993(98)00989-5.
42. Das, D., Luo, X., Singh, A., Gu, Y., Ghosh, S., Mukhopadhyay, C. K., et al. (2010). Paradoxical role of prion protein aggregates in redox-iron induced toxicity. PLoS ONE5: e11420. doi: 10. 1371/journal. pone. 0011420.
43. Davalos, D., Ryu, J. K., Merlini, M., Baeten, K. M., Le Moan, N., Petersen, M. A., et al. (2012). Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat. Commun. 3, 1227. doi: 10. 1038/ncomms2230.
44. de Lima, M. N., Polydoro, M., Laranja, D. C., Bonatto, F., Bromberg, E., Moreira, J. C., et al. (2005). Recognition memory impairment and brain oxidative stress induced by postnatal iron administration. Eur. J. Neurosci. 21, 2521-2528. doi: 10. 1111/j. 1460-9568. 2005. 04083. x.
45. Depalma, R. G., Hayes, V. W., Chow, B. K., Shamayeva, G., May, P. E., and Zacharski, L. R. (2010). Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. J. Vasc. Surg. 51, 1498-1503. doi: 10. 1016/j. jvs. 2009. 12. 068.
46. Diomedi, M., and Misaggi, G. (2013). Vascular contribution to Alzheimer disease: predictors of rapid progression. CNS Neurol. Disord. Drug Targets 12, 532-537.
47. Dudonne, S., Vitrac, X., Coutiere, P., Woillez, M., and Merillon, J. M. (2009). Comparative study of antioxidant properties and total phenolic content of 30 plant extracts of industrial interest using DPPH, ABTS, FRAP, SOD, and ORAC assays. J. Agric. Food Chem. 57, 1768-1774. doi: 10. 1021/jf803011r.
48. Duley, L., Matar, H. E., Almerie, M. Q., and Hall, D. R. (2010). Alternative magnesium sulphate regimens for women with pre-eclampsia and eclampsia. Cochrane Database Syst. Rev. (8): CD007388. doi: 10. 1002/14651858. CD007388. pub2.
49. Durlach, J. (1990). Magnesium depletion and pathogenesis of Alzheimer's disease. Magnes. Res. 3, 217-218.
50. Egyud, L. G., and Lipinski, B. (1991). Significance of fibrin formation and dissolution in the pathogenesis and treatment of cancer. Med. Hypotheses 36, 336-340. doi: 10. 1016/0306-9877(91)90006-K.
51. Elin, R. J. (1994). Magnesium: the fifth but forgotten electrolyte. Am. J. Clin. Pathol. 102, 616-622.
52. Eltzschig, H. K., and Carmeliet, P. (2011). Hypoxia and inflammation. N. Engl. J. Med. 364, 656-665. doi: 10. 1056/NEJMra0910283.
53. Erikssen, G., Liestol, K., Bjornholt, J. V., Stormorken, H., Thaulow, E., and Erikssen, J. (2000). Erythrocyte sedimentation rate: a possible marker of atherosclerosis and a strong predictor of coronary heart disease mortality. Eur. Heart J. 21, 1614-1620. doi: 10. 1053/euhj. 2000. 2148.
54. Fawcett, W. J., Haxby, E. J., and Male, D. A. (1999). Magnesium: physiology and pharmacology. Br. J. Anaesth. 83, 302-320. doi: 10. 1093/bja/83. 2. 302.
55. Feart, C., Alles, B., Merle, B., Samieri, C., and Barberger-Gateau, P. (2012). Adherence to a Mediterranean diet and energy, macro-, and micronutrient intakes in older persons. J. Physiol. Biochem. 68, 691-700. doi: 10. 1007/s13105-012-0190-y.
56. Feart, C., Samieri, C., and Barberger-Gateau, P. (2010). Mediterranean diet and cognitive function in older adults. Curr. Opin. Clin. Nutr. Metab. Care 13, 14-18. doi: 10. 1097/MCO. 0b013e3283331fe4.
57. Fiala, M., Liu, Q. N., Sayre, J., Pop, V., Brahmandam, V., Graves, M. C., et al. (2002). Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier. Eur. J. Clin. Invest. 32, 360-371. doi: 10. 1046/j. 1365-2362. 2002. 00994. x.
58. Galano, A. (2011). On the direct scavenging activity of melatonin towards hydroxyl and a series of peroxyl radicals. Phys. Chem. Chem. Phys. 13, 7178-7188. doi: 10. 1039/c0cp02801k.
59. Grammas, P., Tripathy, D., Sanchez, A., Yin, X., and Luo, J. (2011). Brain microvasculature and hypoxia-related proteins in Alzheimer's disease. Int. J. Clin. Exp. Pathol. 4, 616-627.
60. Grootveld, M., and Halliwell, B. (1986). Aromatic hydroxylation as a potential measure of hydroxyl-radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem. J. 237, 499-504.
61. Gu, Y., Luchsinger, J. A., Stern, Y., and Scarmeas, N. (2010). Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer's disease. J. Alzheimers Dis. 22, 483-492. doi: 10. 3233/JAD-2010-100897.
62. Guerrero-Romero, F., Tamez-Perez, H. E., Gonzalez-Gonzalez, G., Salinas-Martinez, A. M., Montes-Villarreal, J., Trevino-Ortiz, J. H., et al. (2004). Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes Metab. 30, 253-258. doi: 10. 1016/S1262-3636(07)70116-7.
63. Gupta, A., Watkins, A., Thomas, P., Majer, R., Habubi, N., Morris, G., et al. (2005). Coagulation and inflammatory markers in Alzheimer's and vascular dementia. Int. J. Clin. Pract. 59, 52-57. doi: 10. 1111/j. 1742-1241. 2004. 00143. x.
64. Gveric, D., Hanemaaijer, R., Newcombe, J., Van Lent, N. A., Sier, C. F., and Cuzner, M. L. (2001). Plasminogen activators in multiple sclerosis lesions: implications for the inflammatory response and axonal damage. Brain 124, 1978-1988. doi: 10. 1093/brain/124. 10. 1978.
65. Hahalis, G., Kalogeropoulos, A., Terzis, G., Tselepis, A. D., Kourakli, A., Mylona, P., et al. (2011). Premature atherosclerosis in non-transfusion-dependent beta-thalassemia intermedia. Cardiology 118, 159-163. doi: 10. 1159/000327997.
66. Houston, M. (2011). The role of magnesium in hypertension and cardiovascular disease. J. Clin. Hypertens (Greenwich) 13, 843-847. doi: 10. 1111/j. 1751-7176. 2011. 00538. x.
67. Hu, N., Yu, J. T., Tan, L., Wang, Y. L., Sun, L., and Tan, L. (2013). Nutrition and the risk of Alzheimer's disease. Biomed. Res. Int. 2013, 524820. doi: 10. 1155/2013/524820.
68. Huang, J. H., Lu, Y. F., Cheng, F. C., Lee, J. N., and Tsai, L. C. (2012). Correlation of magnesium intake with metabolic parameters, depression and physical activity in elderly type 2 diabetes patients: a cross-sectional study. Nutr. J. 11, 41. doi: 10. 1186/1475-2891-11-41.
69. Hultman, K., Strickland, S., and Norris, E. H. (2013). The APOE varepsilon4/varepsilon4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer's disease patients. J. Cereb. Blood Flow Metab. 33, 1251-1258. doi: 10. 1038/jcbfm. 2013. 76.
70. Huntsman, R. G., Hurn, B. A., and Lehmann, H. (1960). Observations on the effect of magnesium on blood coagulation. J. Clin. Pathol. 13, 99-101. doi: 10. 1136/jcp. 13. 2. 99.
71. Inoue, A., Koh, C. S., Yamazaki, M., Yanagisawa, N., Ishihara, Y., and Kim, B. S. (1997). Fibrin deposition in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease. J. Neuroimmunol. 77, 185-194. doi: 10. 1016/S0165-5728(97)00072-6.
72. Issa, A. M., Mojica, W. A., Morton, S. C., Traina, S., Newberry, S. J., Hilton, L. G., et al. (2006). The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: a systematic review. Dement. Geriatr. Cogn. Disord. 21, 88-96. doi: 10. 1159/000090224.
73. Kahle, K., Huemmer, W., Kempf, M., Scheppach, W., Erk, T., and Richling, E. (2007). Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption. J. Agric. Food Chem. 55, 10605-10614. doi: 10. 1021/jf071942r.
74. Kalaria, R. N. (2003). Vascular factors in Alzheimer's disease. Int. Psychogeriatr. 15(Suppl. 1), 47-52. doi: 10. 1017/S1041610203008950.
75. Kaur, J., Zhao, Z., Klein, G. M., Lo, E. H., and Buchan, A. M. (2004). The neurotoxicity of tissue plasminogen activator? J. Cereb. Blood Flow Metab. 24, 945-963. doi: 10. 1097/01. WCB. 0000137868. 50767. E8.
76. Ke, Y., and Ming Qian, Z. (2003). Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol. 2, 246-253. doi: 10. 1016/S1474-4422(03)00353-3.
77. Kell, D. B. (2010). Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples. Arch. Toxicol. 84, 825-889. doi: 10. 1007/s00204-010-0577-x.
78. Kesse-Guyot, E., Andreeva, V. A., Lassale, C., Ferry, M., Jeandel, C., Hercberg, S., et al. (2013). Mediterranean diet and cognitive function: a French study. Am. J. Clin. Nutr. 97, 369-376. doi: 10. 3945/ajcn. 112. 047993.
79. Kiechl, S., Willeit, J., Egger, G., Poewe, W., and Oberhollenzer, F. (1997). Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 96, 3300-3307. doi: 10. 1161/01. CIR. 96. 10. 3300.
80. Kim, D. J., Xun, P., Liu, K., Loria, C., Yokota, K., Jacobs, D. R. Jr., et al. (2010). Magnesium intake in relation to systemic inflammation, insulin resistance, and the incidence of diabetes. Diabetes Care 33, 2604-2610. doi: 10. 2337/dc10-0994.
81. King, A. (2013). Prevention: the benefits of a Mediterranean diet. Nat. Rev. Cardiol. 10, 239. doi: 10. 1038/nrcardio. 2013. 36.
82. Kling, M. A., Trojanowski, J. Q., Wolk, D. A., Lee, V. M. A., and Arnold, S. E. (2013). Vascular disease and dementias: paradigm shifts to drive research in new directions. Alzheimers Dement. 9, 76-92. doi: 10. 1016/j. jalz. 2012. 02. 007.
83. Kovacic, J. C., and Fuster, V. (2012). Atherosclerotic risk factors, vascular cognitive impairment, and Alzheimer disease. Mt. Sinai J. Med. 79, 664-673. doi: 10. 1002/msj. 21347.
84. Krstic, D., and Knuesel, I. (2013). Deciphering the mechanism underlying late-onsetalzheimer disease. Nat. Rev. Neurol. 9, 25-34. doi: 10. 1038/nrneurol. 2012. 236.
85. Kruszewski, M. (2003). Labile iron pool: the main determinant of cellular response to oxidative stress. Mutat. Res. 531, 81-92. doi: 10. 1016/j. mrfmmm. 2003. 08. 004.
86. Kumar, S., Okello, E. J., and Harris, J. R. (2012). Experimental inhibition of fibrillogenesis and neurotoxicity by amyloid-beta (Abeta) and other disease-related peptides/proteins by plant extracts and herbal compounds. Subcell. Biochem. 65, 295-326. doi: 10. 1007/978-94-007-5416-4_13.
87. Kupetsky-Rincon, E. A., and Uitto, J. (2012). Magnesium: novel applications in cardiovascular disease-a review of the literature. Ann. Nutr. Metab. 61, 102-110. doi: 10. 1159/000339380.
88. Kwan, A. H., Winefield, R. D., Sunde, M., Matthews, J. M., Haverkamp, R. G., Templeton, M. D., et al. (2006). Structural basis for rodlet assembly in fungal hydrophobins. Proc. Natl. Acad. Sci. U. S. A. 103, 3621-3626. doi: 10. 1073/pnas. 0505704103.
89. Larsson, S. C., Orsini, N., and Wolk, A. (2012). Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am. J. Clin. Nutr. 95, 362-366. doi: 10. 3945/ajcn. 111. 022376.
90. Lee, J. E., and Han, P. L. (2013). An update of animal models of Alzheimer disease with a reevaluation of plaque depositions. Exp. Neurobiol. 22, 84-95. doi: 10. 5607/en. 2013. 22. 2. 84.
91. Limaye, C. S., Londhey, V. A., Nadkart, M. Y., and Borges, N. E. (2011). Hypomagnesemia in critically ill medical patients. J. Assoc. Physicians India 59, 19-22.
92. Lin, B. (2011). Polyphenols and neuroprotection against ischemia and neurodegeneration. Mini Rev. Med. Chem. 11, 1222-1238. doi: 10. 2174/138955711804586784.
93. Lipinska, I., Lipinski, B., Gurewich, V., and Hoffmann, K. D. (1976). Fibrinogen heterogeneity in cancer, in occlusive vascular disease, and after surgical procedures. Am. J. Clin. Pathol. 66, 958-966.
94. Lipinski, B. (2001). Pathophysiology of oxidative stress in diabetes mellitus. J. Diabetes Complicat. 15, 203-210. doi: 10. 1016/S1056-8727(01)00143-X.
95. Lipinski, B. (2011). Hydroxyl radical and its scavengers in health and disease. Oxid. Med. Cell. Longev. 2011, 809696. doi: 10. 1155/2011/809696.
96. Lipinski, B., and Pretorius, E. (2012). Novel pathway of ironinduced blood coagulation: implications for diabetes mellitus and its complications. Pol. Arch. Med. Wewn. 122, 115-122.
97. Lipinski, B., and Pretorius, E. (2013). Iron-induced fibrin in cardiovascular disease. Curr. Neurovasc. Res. 10, 269-274. doi: 10. 2174/15672026113109990016.
98. Lipinski, B., and Sajdel-Sulkowska, E. M. (2006). New insight into Alzheimer disease: demonstration of fibrin(ogen)-serum albumin insoluble deposits in brain tissue. Alzheimer Dis. Assoc. Disord. 20, 323-326. doi: 10. 1097/01. wad. 0000213844. 21001. a2.
99. Lipinski, B., Worowski, K., Mysliwiec, M., and Farbiszewski, R. (1969). Erythrocyte sedimentation and soluble fibrin monomer complexes. Thromb. Diath. Haemorrh. 21, 196-202.
100. Lonergan, P. E., Martin, D. S., Horrobin, D. F., and Lynch, M. A. (2002). Neuroprotective effect of eicosapentaenoic acid in hippocampus of rats exposed to gamma-irradiation. J. Biol. Chem. 277, 20804-20811. doi: 10. 1074/jbc. M202387200.
101. Lourida, I., Soni, M., Thompson-Coon, J., Purandare, N., Lang, I. A., Ukoumunne, O. C., et al. (2013). Mediterranean diet, cognitive function, and dementia: a systematic review. Epidemiology 24, 479-489. doi: 10. 1097/EDE. 0b013e3182944410.
102. Lukiw, W. J., and Bazan, N. G. (2008). Docosahexaenoic acid and the aging brain. J. Nutr. 138, 2510-2514. doi: 10. 3945/jn. 108. 096016.
103. Mandel, S., Amit, T., Reznichenko, L., Weinreb, O., and Youdim, M. B. (2006). Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Mol. Nutr. Food Res. 50, 229-234. doi: 10. 1002/mnfr. 200500156.
104. Markesbery, W. R., and Carney, J. M. (1999). Oxidative alterations in Alzheimer's disease. Brain Pathol. 9, 133-146. doi: 10. 1111/j. 1750-3639. 1999. tb00215. x.
105. Marszalek, J. R., and Lodish, H. F. (2005). Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu. Rev. Cell Dev. Biol. 21, 633-657. doi: 10. 1146/annurev. cellbio. 21. 122303. 120624.
106. Mazur, A., Maier, J. A., Rock, E., Gueux, E., Nowacki, W., and Rayssiguier, Y. (2007). Magnesium and the inflammatory response: potential physiopathological implications. Arch. Biochem. Biophys. 458, 48-56. doi: 10. 1016/j. abb. 2006. 03. 031.
107. McDonald, S. D., Lutsiv, O., Dzaja, N., and Duley, L. (2012). A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. Int. J. Gynaecol. Obstet. 118, 90-96. doi: 10. 1016/j. ijgo. 2012. 01. 028.
108. McIntosh, T. K., Vink, R., Yamakami, I., and Faden, A. I. (1989). Magnesium protects against neurological deficit after brain injury. Brain Res. 482, 252-260. doi: 10. 1016/0006-8993(89)91188-8.
109. Melcher, K. (2004). New chemical crosslinking methods for the identification of transient protein-protein interactions with multiprotein complexes. Curr. Protein Pept. Sci. 5, 287-296. doi: 10. 2174/1389203043379701.
110. Meng, F., Abedini, A., Plesner, A., Verchere, C. B., and Raleigh, D. P. (2010). The flavanol (-)-epigallocatechin 3-gallate inhibits amyloid formation by islet amyloid polypeptide, disaggregates amyloid fibrils, and protects cultured cells against IAPP-induced toxicity. Biochemistry 49, 8127-8133. doi: 10. 1021/bi100939a.
111. Merkle, D. L., Cheng, C. H., Castellino, F. J., and Chibber, B. A. (1996). Modulation of fibrin assembly and polymerization by the beta-amyloid of Alzheimer's disease. Blood Coagul. Fibrinolysis 7, 650-658. doi: 10. 1097/00001721-199609000-00011.
112. Merono, T., Rosso, L. G., Sorroche, P., Boero, L., Arbelbide, J., and Brites, F. (2011). High risk of cardiovascular disease in iron overload patients. Eur. J. Clin. Invest. 41, 479-486. doi: 10. 1111/j. 1365-2362. 2010. 02429. x.
113. Milte, C. M., Sinn, N., and Howe, P. R. (2009). Polyunsaturated fatty acid status in attention deficit hyperactivity disorder, depression, and Alzheimer's disease: towards an omega-3 index for mental health? Nutr. Rev. 67, 573-590. doi: 10. 1111/j. 1753-4887. 2009. 00229. x.
114. Mohanty, J. G., Eckley, D. M., Williamson, J. D., Launer, L. J., and Rifkind, J. M. (2008). Do red blood cell-beta-amyloid interactions alter oxygen delivery in Alzheimer's disease? Adv. Exp. Med. Biol. 614, 29-35. doi: 10. 1007/978-0-387-74911-2_4.
115. Moreira, P. I., Honda, K., Liu, Q., Santos, M. S., Oliveira, C. R., Aliev, G., et al. (2005). Oxidative stress: the old enemy in Alzheimer's disease pathophysiology. Curr. Alzheimer Res. 2, 403-408. doi: 10. 2174/156720505774330537.
116. Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C., Bennett, D. A., Wilson, R. S., et al. (2003). Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch. Neurol. 60, 940-946. doi: 10. 1001/archneur. 60. 7. 940.
117. Muir, K. W., Lees, K. R., Ford, I., and Davis, S. (2004). Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet363, 439-445. doi: 10. 1016/S0140-6736(04)15490-1.
118. Multhaup, K. S. (1995). Aging, source, and decision criteria: when false fame errors do and do not occur. Psychol. Aging 10, 492-497. doi: 10. 1037/0882-7974. 10. 3. 492.
119. Muroi, C., Burkhardt, J. K., Hugelshofer, M., Seule, M., Mishima, K., and Keller, E. (2012). Magnesium and the inflammatory response: potential pathophysiological implications in the management of patients with aneurysmal subarachnoid hemorrhage? Magnes. Res. 25, 64-71.
120. Mussoni, L., Sironi, L., Tedeschi, L., Calvio, A. M., Colli, S., and Tremoli, E. (2001). Magnesium inhibits arterial thrombi after vascular injury in rat: in vivo impairment of coagulation. Thromb. Haemost. 86, 1292-1295.
121. Nagy, E., Eaton, J. W., Jeney, V., Soares, M. P., Varga, Z., Galajda, Z., et al. (2010). Red cells, hemoglobin, heme, iron, and atherogenesis. Arterioscler. Thromb. Vasc. Biol. 30, 1347-1353. doi: 10. 1161/ATVBAHA. 110. 206433.
122. Nakajima, Y., Masaoka, N., Hayakawa, Y., Watanabe, M., Nagaishi, M., Sakata, H., et al. (2006). The production of hydroxyl radicals in the fetal lamb brain resulting from occlusion of the umbilical circulation and the transplacental effect of MCI-186 to inhibit hydroxyl radical production. Pediatr. Res. 59, 216-220. doi: 10. 1203/01. pdr. 0000196373. 52086. c2.
123. Natali, A., L'Abbate, A., and Ferrannini, E. (2003). Erythrocyte sedimentation rate, coronary atherosclerosis, and cardiac mortality. Eur. Heart J. 24, 639-648. doi: 10. 1016/S0195-668X(02)00741-8.
124. Ninomia, T., Wang, L., Kumar, S. R., Kim, A., and Zlokovic, B. V. (2000). Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model. J. Cereb. Blood Flow Metab. 20, 998-1009. doi: 10. 1097/00004647-200006000-00012.
125. Nunomura, A., Perry, G., Aliev, G., Hirai, K., Takeda, A., Balraj, E. K., et al. (2001). Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol. 60, 759-767.
126. Okereke, E., Ahonsi, B., Tukur, J., Ishaku, S. M., and Oginni, A. B. (2012). Benefits of using magnesium sulphate (MgSO(4) for eclampsia management and maternal mortality reduction: lessons from Kano State in Northern Nigeria. BMC Res. Notes5: 421. doi: 10. 1186/1756-0500-5-421.
127. Palhano, F. L., Lee, J., Grimster, N. P., and Kelly, J. W. (2013). Toward the molecular mechanism(s) by which EGCG treatment remodels mature amyloid fibrils. J. Am. Chem. Soc. 135, 7503-7510. doi: 10. 1021/ja3115696.
128. Palmblad, J. (2010). The acute inflammatory reaction: the legacy of Mechnikov. J. Intern. Med. 268, 35-37.
129. Paul, J., Strickland, S., and Melchor, J. P. (2007). Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer's disease. J. Exp. Med. 204, 1999-2008. doi: 10. 1084/jem. 20070304.
130. Peers, C., Pearson, H. A., and Boyle, J. P. (2007). Hypoxia and Alzheimer's disease. Essays Biochem. 43, 153-164. doi: 10. 1042/BSE0430153.
131. Pimplikar, S. W. (2009). Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int. J. Biochem. Cell Biol. 41, 1261-1268. doi: 10. 1016/j. biocel. 2008. 12. 015.
132. Pretorius, E., Bester, J., Vermeulen, N., and Lipinski, B. (2013a). Oxidation inhibits iron-induced blood coagulation. Curr. Drug Targets 14, 13-19. doi: 10. 2174/138945013804806541.
133. Pretorius, E., Vermeulen, N., Bester, J., Lipinski, B., and Kell, D. B. (2013b). A novel method for assessing the role of iron and its functional chelation in fibrin fibril formation: the use of scanning electron microscopy. Toxicol. Mech. Methods 23, 352-359. doi: 10. 3109/15376516. 2012. 762082.
134. Pretorius, E., and Lipinski, B. (2013). Iron alters red blood cell morphology. Blood121, 9. doi: 10. 1182/blood-2012-09-454793.
135. Ravn, H. B., Kristensen, S. D., Hjortdal, V. E., Thygesen, K., and Husted, S. E. (1997). Early administration of intravenous magnesium inhibits arterial thrombus formation. Arterioscler. Thromb. Vasc. Biol. 17, 3620-3625. doi: 10. 1161/01. ATV. 17. 12. 3620.
136. Ray, B., and Lahiri, D. K. (2009). Neuroinflammation in Alzheimer's disease: different molecular targets and potential therapeutic agents including curcumin. Curr. Opin. Pharmacol. 9, 434-444. doi: 10. 1016/j. coph. 2009. 06. 012.
137. Reffelmann, T., Ittermann, T., Dorr, M., Volzke, H., Reinthaler, M., Petersmann, A., et al. (2011). Low serum magnesium concentrations predict cardiovascular and all-cause mortality. Atherosclerosis 219, 280-284. doi: 10. 1016/j. atherosclerosis. 2011. 05. 038.
138. Ringman, J. M., Frautschy, S. A., Cole, G. M., Masterman, D. L., and Cummings, J. L. (2005). A potential role of the curry spice curcumin in Alzheimer's disease. Curr. Alzheimer Res. 2, 131-136. doi: 10. 2174/1567205053585882.
139. Robinson, D., Bucci, J., Fenn, H., Miller, T., Tinklenberg, J., and Yesavage, J. A. (1995). Erythrocyte sedimentation rate in Alzheimer's dementia. J. Am. Geriatr. Soc. 43, 1177-1178.
140. Rodriguez-Moran, M., and Guerrero-Romero, F. (2003). Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care 26, 1147-1152. doi: 10. 2337/diacare. 26. 4. 1147.
141. Romani, A. M. (2013). Magnesium homeostasis in mammalian cells. Met. Ions Life Sci. 12, 69-118. doi: 10. 1007/978-94-007-5561-1_4.
142. Rossi, L., Mazzitelli, S., Arciello, M., Capo, C. R., and Rotilio, G. (2008). Benefits from dietary polyphenols for brain aging and Alzheimer's disease. Neurochem. Res. 33, 2390-2400. doi: 10. 1007/s11064-008-9696-7.
143. Rowe, W. J. (2012). Correcting magnesium deficiencies may prolong life. Clin. Interv. Aging 7, 51-54. doi: 10. 2147/CIA. S28768.
144. Saini, A. K., Kumar, H. S. A., and Sharma, S. S. (2007). Preventive and curative effect of edaravone on nerve functions and oxidative stress in experimental diabetic neuropathy. Eur. J. Pharmacol. 568, 164-172. doi: 10. 1016/j. ejphar. 2007. 04. 016.
145. Scarmeas, N., Stern, Y., Mayeux, R., and Luchsinger, J. A. (2006). Mediterranean diet, Alzheimer disease, and vascular mediation. Arch. Neurol. 63, 1709-1717. doi: 10. 1001/archneur. 63. 12. noc60109.
146. Schneider, J. A., Arvanitakis, Z., Bang, W., and Bennett, D. A. (2007). Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69, 2197-2204. doi: 10. 1212/01. wnl. 0000271090. 28148. 24.
147. Sery, O., Povova, J., Misek, I., Pesak, L., and Janout, V. (2013). Molecular mechanisms of neuropathological changes in Alzheimer's disease: a review. Folia Neuropathol. 51, 1-9. doi: 10. 5114/fn. 2013. 34190.
148. Shechter, M. (2010). Magnesium and cardiovascular system. Magnes. Res. 23, 60-72.
149. Silvestri, L., and Camaschella, C. (2008). A potential pathogenetic role of iron in Alzheimer's disease. J. Cell. Mol. Med. 12, 1548-1550. doi: 10. 1111/j. 1582-4934. 2008. 00356. x.
150. Sinn, N., Milte, C., and Howe, P. R. (2010). Oiling the brain: a review of randomized controlled trials of omega-3 fatty acids in psychopathology across the lifespan. Nutrients 2, 128-170. doi: 10. 3390/nu2020128.
151. Skaper, S. D. (2012). Alzheimer's disease and amyloid: culprit or coincidence? Int. Rev. Neurobiol. 102, 277-316. doi: 10. 1016/B978-0-12-386986-9. 00011-9.
152. Slutsky, I., Abumaria, N., Wu, L. J., Huang, C., Zhang, L., Li, B., et al. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron 65, 165-177. doi: 10. 1016/j. neuron. 2009. 12. 026.
153. Smith, M. A., Zhu, X., Tabaton, M., Liu, G., Mckeel, D. W. Jr., Cohen, M. L., et al. (2010). Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J. Alzheimers Dis. 19, 363-372. doi: 10. 3233/JAD-2010-1239.
154. Song, C., Leonard, B. E., and Horrobin, D. F. (2004). Dietary ethyl-eicosapentaenoic acid but not soybean oil reverses central interleukin-1-induced changes in behavior, corticosterone and immune response in rats. Stress 7, 43-54. doi: 10. 1080/10253890410001667188.
155. Squier, T. C. (2001). Oxidative stress and protein aggregation during biological aging. Exp. Gerontol. 36, 1539-1550. doi: 10. 1016/S0531-5565(01)00139-5.
156. Squitti, R. (2012). Metals in Alzheimer's disease: a systemic perspective. Front. Biosci. 17: 451-472. doi: 10. 2741/3938.
157. Srinivasan, M., Sudheer, A. R., and Menon, V. P. (2007). Ferulic acid: therapeutic potential through its antioxidant property. J. Clin. Biochem. Nutr. 40, 92-100. doi: 10. 3164/jcbn. 40. 92.
158. Srinivasan, V., Pandi-Perumal, S. R., Maestroni, G. J., Esquifino, A. I., Hardeland, R., and Cardinali, D. P. (2005). Role of melatonin in neurodegenerative diseases. Neurotox. Res. 7, 293-318. doi: 10. 1007/BF03033887.
159. Srividhya, R., Jyothilakshmi, V., Arulmathi, K., Senthilkumaran, V., and Kalaiselvi, P. (2008). Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate. Int. J. Dev. Neurosci. 26, 217-223. doi: 10. 1016/j. ijdevneu. 2007. 12. 003.
160. Srividhya, R., and Kalaiselvi, P. (2013). Neuroprotective potential of epigallo catechin-3-gallate in PC-12 cells. Neurochem. Res. 38, 486-493. doi: 10. 1007/s11064-012-0940-9.
161. Stankiewicz, J. M., and Brass, S. D. (2009). Role of iron in neurotoxicity: a cause for concern in the elderly? Curr. Opin. Clin. Nutr. Metab. Care 12, 22-29. doi: 10. 1097/MCO. 0b013e32831ba07c.
162. Steinhubl, S. R. (2008). Why have antioxidants failed in clinical trials? Am. J. Cardiol. 101, 14D-19D. doi: 10. 1016/j. amjcard. 2008. 02. 003.
163. Stern, R. A., Trojanowski, J. Q., and Lee, V. M. (1990). Antibodies to the beta-amyloid peptide cross-react with conformational epitopes in human fibrinogen subunits from peripheral blood. FEBS Lett. 264, 43-47. doi: 10. 1016/0014-5793(90)80760-G.
164. Summers, W. K. (2004). Alzheimer's disease, oxidative injury, and cytokines. J. Alzheimers Dis. 6, 651-657; discussion 673-681.
165. Szweda, P. A., Friguet, B., and Szweda, L. I. (2002). Proteolysis, free radicals, and aging. Free Radic. Biol. Med. 33, 29-36. doi: 10. 1016/S0891-5849(02)00837-7.
166. Tateishi, N., Suzuki, Y., Cicha, I., and Maeda, N. (2001). O(2) release from erythrocytes flowing in a narrow O(2)-permeable tube: effects of erythrocyte aggregation. Am. J. Physiol. Heart Circ. Physiol. 281, H448-H456.
167. Thaipisuttikul, P., and Galvin, J. E. (2012). Use of medical foods and nutritional approaches in the treatment of Alzheimer's disease. Clin. Pract. (Lond.) 9, 199-209. doi: 10. 2217/cpr. 12. 3.
168. Thomas, M., and Jankovic, J. (2004). Neurodegenerative disease and iron storage in the brain. Curr. Opin. Neurol. 17, 437-442. doi: 10. 1097/01. wco. 0000137534. 61244. d1.
169. Touyz, R. M. (2004). Magnesium in clinical medicine. Front. Biosci. 9: 1278-1293. doi: 10. 2741/1316.
170. Tripathy, D., Sanchez, A., Yin, X., Luo, J., Martinez, J., and Grammas, P. (2013). Thrombin, a mediator of cerebrovascular inflammation in AD and hypoxia. Front. Aging Neurosci. 5: 19. doi: 10. 3389/fnagi. 2013. 00019.
171. Tully, A. M., Roche, H. M., Doyle, R., Fallon, C., Bruce, I., Lawlor, B., et al. (2003). Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Br. J. Nutr. 89, 483-489. doi: 10. 1079/BJN2002804.
172. Tuppo, E. E., and Arias, H. R. (2005). The role of inflammation in Alzheimer's disease. Int. J. Biochem. Cell Biol. 37, 289-305. doi: 10. 1016/j. biocel. 2004. 07. 009.
173. Ueno, S., Kashimoto, T., Susa, N., Wada, K., Ito, N., Takeda-Homma, S., et al. (2006). Estimation of hydroxyl radical generation by salicylate hydroxylation method in multiple organs of mice exposed to whole-body X-ray irradiation. Free Radic. Res. 40, 944-951. doi: 10. 1080/10715760600817963.
174. van Oijen, M., Witteman, J. C., Hofman, A., Koudstaal, P. J., and Breteler, M. M. (2005). Fibrinogen is associated with an increased risk of Alzheimer disease and vascular dementia. Stroke 36, 2637-2641. doi: 10. 1161/01. STR. 0000189721. 31432. 26.
175. van Oss, C. J. (1990). Surface properties of fibrinogen and fibrin. J. Protein Chem. 9, 487-491. doi: 10. 1007/BF01024625.
176. Vassallo, N., and Scerri, C. (2013). Mediterranean diet and dementia of the Alzheimer type. Curr. Aging Sci. 6, 150-162.
177. Vignini, A., Giulietti, A., Nanetti, L., Raffaelli, F., Giusti, L., Mazzanti, L., et al. (2013). Alzheimer's disease and diabetes: new insights and unifying therapies. Curr. Diabetes Rev. 9, 218-227. doi: 10. 2174/1573399811309030003.
178. Wang, J., Ferruzzi, M. G., Ho, L., Blount, J., Janle, E. M., Gong, B., et al. (2012). Brain-targeted proanthocyanidin metabolites for Alzheimer's disease treatment. J. Neurosci. 32, 5144-5150. doi: 10. 1523/JNEUROSCI. 6437-11. 2012.
179. Watanabe, M., Suga, T., Yoshioka, K., Doi, M., Chiba, M., and Ogawa, A. (1996). [A case of acute occlusion of left middle cerebral artery due to an embolus treated successfully with percutaneous transluminal angioplasty]. No Shinkei Geka 24, 1027-1032.
180. Weglicki, W. B. (2012). Hypomagnesemia and inflammation: clinical and basic aspects. Annu. Rev. Nutr. 32, 55-71. doi: 10. 1146/annurev-nutr-071811-150656.
181. Weinberg, E. D. (2010). The hazards of iron loading. Metallomics 2, 732-740. doi: 10. 1039/c0mt00023j.
182. Woolf, N. (1961). The distribution of fibrin within the aortic intima. An immunohistochemical study. Am. J. Pathol. 39, 521-532.
183. Woollard, K. J., Sturgeon, S., Chin-Dusting, J. P., Salem, H. H., and Jackson, S. P. (2009). Erythrocyte hemolysis and hemoglobin oxidation promote ferric chloride-induced vascular injury. J. Biol. Chem. 284, 13110-13118. doi: 10. 1074/jbc. M809095200.
184. Wyss-Coray, T., and Rogers, J. (2012). Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med. 2, a006346. doi: 10. 1101/cshperspect. a006346.
185. Yan, Y., Gong, K., Ma, T., Zhang, L., Zhao, N., Zhang, X., et al. (2012). Protective effect of edaravone against Alzheimer's disease-relevant insults in neuroblastoma N2a cells. Neurosci. Lett. 531, 160-165. doi: 10. 1016/j. neulet. 2012. 10. 043.
186. Yarchoan, M., Xie, S. X., Kling, M. A., Toledo, J. B., Wolk, D. A., Lee, E. B., et al. (2012). Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 135, 3749-3756. doi: 10. 1093/brain/aws271.
187. Yavin, E., Brand, A., and Green, P. (2002). Docosahexaenoic acid abundance in the brain: a biodevice to combat oxidative stress. Nutr. Neurosci. 5, 149-157. doi: 10. 1080/10284150290003159.
188. Yehuda, S., Rabinovtz, S., Carasso, R. L., and Mostofsky, D. I. (1996). Essential fatty acids preparation (SR-3) improves Alzheimer's patients quality of life. Int. J. Neurosci. 87, 141-149. doi: 10. 3109/00207459609070833.
189. Zamolodchikov, D., and Strickland, S. (2012). Abeta delays fibrin clot lysis by altering fibrin structure and attenuating plasminogen binding to fibrin. Blood 119, 3342-3351. doi: 10. 1182/blood-2011-11-389668.
190. Zhao, L. N., Chiu, S. W., Benoit, J., Chew, L. Y., and Mu, Y. (2012). The effect of curcumin on the stability of Abeta dimers. J. Phys. Chem. B 116, 7428-7435. doi: 10. 1021/jp3034209.
191. Zheng, W., and Monnot, A. D. (2012). Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases. Pharmacol. Ther. 133, 177-188. doi: 10. 1016/j. pharmthera. 2011. 10. 006.
192. Zielonka, J., Gebicki, J., and Grynkiewicz, G. (2003). Radical scavenging properties of genistein. Free Radic. Biol. Med. 35, 958-965. doi: 10. 1016/S0891-5849(03)00472-6.