Docosahexaenoic acid and amyloid-β peptide signaling in alzheimer's disease

World Review of Nutrition and Dietetics

Volumn 99, Issue , 2009, Pages 55-70

  Lukiw, Walter J ^a  

^a LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; CHOLESTEROL; DOCOSAHEXAENOIC ACID;

ALZHEIMER DISEASE; APOPTOSIS; HUMAN; INFLAMMATION; METABOLISM; OXIDATIVE STRESS; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; APOPTOSIS; CHOLESTEROL; DOCOSAHEXAENOIC ACIDS; HUMANS; INFLAMMATION; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 62449332070     PISSN: 00842230     EISSN: 16623975     Source Type: Book Series    
DOI: 10.1159/000192996     Document Type: Article

References (148)

1. Beal MF: Mitochondria, free radicals, and neurode-generation. Curr Opin Neurol 1996;6:661-666.
2. Pappolla MA, Omar RA, Kim KS, Robakis NK: Immunohistochemical evidence of oxidative stress in Alzheimer's disease. Am J Pathol 1992;140:621- 628.
3. Pappolla MA, Chyan YJ, Omar RA, Hsiao K, Perry G, Smith MA, Bozner P: Evidence of oxidative stress and in vivo neurotoxicity of β-amyloid in a trans-genic mouse model of Alzheimer's disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo. Am J Pathol 1998;152:871-877.
4. Lukiw WJ, Bazan NG: Neuroinflammatory signaling up-regulation in Alzheimer's disease. Neurochem Res 2000;25:1173-1184.
5. Butterfield DA: Amyloid β-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. Free Radic Res 2002;36:1307-1313.
6. Butterfield DA, Lauderback CM: Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid β-peptide-associated free radical oxidative stress. Free Radic Biol Med 2002;32:1050-1060.
7. Mattson MP: Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease. J Neurovirol 2002;8:539-550.
8. Mattson M P, Culmsee C, Yu ZF, Camandola S: Roles of nuclear factor-κB in neuronal survival and plasticity. J Neurochem 2000;74:443-456.
9. Aliev G, Smith MA, Obrenovich ME, de la Torre JC, Perry G: Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Alzheimer disease. Neurotox Res 2003;5:491-504.
10. Chaney MO, Baudry J, Esh C, Childress J, Luehrs DC, Kokjohn TA, Roher AE: A beta, aging, and Alzheimer's disease: a tale, models, and hypotheses. Neurol Res 2003;25:581-589.
11. Fam SS, Morrow JD: The isoprostanes: unique products of arachidonic acid oxidation - a review. Curr Med Chem 2003;10:1723-1740.
12. Lynch AM, Moore M, Craig S, Lonergan PE, Martin DS, Lynch MA: Analysis of interleukin-1β-induced cell signaling activation in rat hippocampus following exposure to gamma irradiation. Protective effect of eicosapentaenoic acid. J Biol Chem 2003;278: 51075-51084.
13. Brigelius-Flohe R, Banning A, Kny M, Bol GF: Redox events in interleukin-1 signaling. Arch Biochem Biophys 2004;423:66-73.
14. Leuner K, Hauptmann S, Abdel-Kader R, Scherping I, Keil U, Strosznajder JB, Eckert A, Muller WE: Mitochondrial dysfunction: the first domino in brain aging and Alzheimer's disease? Antioxid Redox Signal 2007;9:1659-1675.
15. Lukiw WJ: Gene expression profiling in fetal, aged and Alzheimer hippocampus - a continuum of stress-related signaling. Neurochem Res 2004;29: 1287-1297.
16. Montine KS, Quinn JF, Zhang J, Fessel J P, Roberts LJ 2nd, Morrow JD, Montine TJ: Isoprostanes and related products of lipid peroxidation in neurode-generative diseases. Chem Phys Lipids 2004;128:117- 124.
17. Alexandrov PN, Zhao Y, Pogue AI, Tarr MA, Kruck T P, Percy ME, Cui JG, Lukiw WJ: Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells. J Alzheimers Dis 2005;8:117-127.
18. Zhao Y, Cui JG, Lukiw WJ: Natural secretory products of human neural and microvessel endothelial cells: implications in pathogenic 'spreading' and Alzheimer's disease. Mol Neurobiol 2006;34:181- 192.
19. Lukiw WJ, Bazan NG: Survival signalling in Alzheimer's disease. Biochem Soc Trans 2006;34: 1277-1282.
20. Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X: Iron: the redox-active center of oxidative stress in Alzheimer disease. Neurochem Res 2007;32:1640-1645.
21. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA: Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001; 60:759-767.
22. Cui JG, Hill JM, Zhao Y, Lukiw WJ: Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer's disease. Neuroreport 2007;18: 115-119.
23. Selkoe D, Kopan R: Notch and presenilin: regulated intramembrane proteolysis links development and degeneration. Annu Rev Neurosci 2003;26:565-597.
24. Selkoe DJ: American College of Physicians; American Physiological Society. Alzheimer disease: mechanistic understanding predicts novel therapies. Ann Intern Med 2004;140:627-638.
25. Cacabelos R, Fernandez-Novoa L, Lombardi V, Corzo L, Pichel V, Kubota Y: Cerebrovascular risk factors in Alzheimer's disease: brain hemodynamics and pharmacogenomic implications. Neurol Res 2003;25:567-580.
26. Fitzpatrick AL, Kuller LH, Ives DG, Lopez OL, Jagust W, Breitner JC, Jones B, Lyketsos C, Dulberg C: Incidence and prevalence of dementia in the Cardiovascular Health Study. J Am Geriatr Soc 2004;52:195-204.
27. Iadecola C: Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci 2004;5:347-360.
28. Hoozemans JJ, Chafekar SM, Baas F, Eikelenboom P, Scheper W: Always around, never the same: pathways of amyloid β-induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease. Curr Med Chem 2006;13:2599-2605.
29. Sidera C, Parsons R, Austen B: Proteolytic cascade in the amyloidogenesis of Alzheimer's disease. Biochem Soc Trans 2004;32:33-36.
30. Hashimoto M, Hossain S, Shimada T, Shido O: Docosahexaenoic acid-induced protective effect against impaired learning in amyloid β-infused rats is associated with increased synaptosomal membrane fluidity. Clin Exp Pharmacol Physiol 2006;33: 934-939.
31. Koo EH: The β-amyloid precursor protein and Alzheimer's disease: does the tail wag the dog? Traffic 2002;3:763-770.
32. Greenberg SM: Cerebral amyloid angiopathy and vessel dysfunction. Cerebrovasc Dis 2002;13(suppl 2):42-47.
33. McGeer EG, McGeer PL: Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:741-749.
34. McGeer PL, Rogers J, McGeer EG: Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years. J Alzheimers Dis 2006;9:271-276.
35. Raina AK, Zhu X, Shimohama S, Perry G, Smith MA: Tipping the apoptotic balance in Alzheimer's disease: the abortosis concept. Cell Biochem Biophys 2003;39:249-255.
36. Monji A, Utsumi H, Ueda T, Imoto T, Yoshida I, Hashioka S, Tashiro K, Tashiro N: Amyloid-β-protein (25-35)-associated free radical generation is strongly influenced by the aggregational state of the peptides. Life Sci 2002;70:833-841.
37. Hajimohamadreza I, Treherne JM: The role of apop-tosis in neurodegenerative diseases. Prog Drug Res 1997;48:55-98.
38. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG: A role for docosahexaenoic acid-derived neuroprotec-tin D1 in neural cell survival and Alzheimer disease. J Clin Invest 2005;115:2774-2783.
39. Lukiw WJ, Pappolla M, Pelaez R P, Bazan NG: Alzheimer's disease - a dysfunction in cholesterol and lipid metabolism. Cell Mol Neurobiol 2005;25: 475-483.
40. Frebel K, Wiese S: Signalling molecules essential for neuronal survival and differentiation. Biochem Soc Trans 2006;34:1287-1290.
41. Lang-Rollin IC, Rideout HJ, Noticewala M, Stefanis L: Mechanisms of caspase-independent neuronal death: energy depletion and free radical generation. J Neurosci 2003;23:11015-11025.
42. Culmsee C, Landshamer S: Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res 2006;3:269-283.
43. Kirkin V, Joos S, Zornig M: The role of Bcl-2 family members. Biochim Biophys Acta 2004;1644:229- 249.
44. Zhu X, Wang Y, Ogawa O, Lee HG, Raina AK, Siedlak SL, Harris PL, Fujioka H, Shimohama S, Tabaton M, Atwood CS, Petersen RB, Perry G, Smith MA: Neuroprotective properties of Bcl-w in Alzheimer disease. J Neurochem 2004;89:1233- 1240.
45. Djaldetti R, Lev N, Melamed E: Neuroprotection in progressive brain disorders. Israeli Med Assoc J 2003;5:576-880.
46. Waldmeier PC: Prospects for antiapoptotic drug therapy of neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 2003;27: 303-321.
47. Huang X, Moir RD, Tanzi RE, Bush AI, Rogers JT: Redox-active metals, oxidative stress, and Alzheimer's disease pathology. Ann NY Acad Sci 2004;1012:153- 163.
48. Facheris M, Beretta S, Ferrarese C: Peripheral markers of oxidative stress and excitotoxicity in neurode-generative disorders: tools for diagnosis and therapy? J Alzheimers Dis 2004;6:177-184.
49. Boedker M, Boetkjaer A, Bazan NG, Cui JG, Zhao Y, Pelaez R P, Lukiw WJ: Budesonide epimer R, LAU-8080 and phenyl butyl nitrone synergistically repress cyclooxygenase-2 induction in [IL-1β + Aβ42]-stressed human neural cells. Neurosci Lett 2005;380:176-180.
50. Boetkjaer A, Boedker M, Cui JG, Zhao Y, Lukiw WJ: Synergism in the repression of COX-2- and TNF-α induction in platelet activating factor-stressed human neural cells. Neurosci Lett 2007;426:59-63.
51. Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN: Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 2003;278:14677- 14687.
52. Hong HS, Hwang EM, Sim HJ, Cho HJ, Boo JH, Oh SS, Kim SU, Mook-Jung I: Interferon-γ stimulates β-secretase expression and sAPPβ production in astrocytes. Biochem Biophys Res Commun 2003; 307:922-927.
53. Hoozemans J, Veerhuis R, Rozemuller A, Eikelenboom P: The pathological cascade of Alzheimer's disease: the role of inflammation and its therapeutic implications. Drugs Today 2002;38: 429-443.
54. Zhang R, Brennan ML, Shen Z, MacPherson JC, Schmitt D, Molenda CE, Hazen SL: Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 2002;277:46116-46122.
55. Bazan NG, Birkle DL, Reddy TS: Docosahexaenoic acid (22:6,n-3) is metabolized to lipoxygenase reaction products in the retina. Biochem Biophys Res Commun 1984;125:741-747.
56. Bazan NG, Colangelo V, Lukiw WJ: Prostaglandins and other lipid mediators in Alzheimer's disease. Prostaglandins Other Lipid Mediat 2002;68-69: 197-210.
57. Reid PC, Urano Y, Kodama T, Hamakubo T: Alzheimer's disease: cholesterol, membrane rafts, isoprenoids and statins. J Cell Mol Med 2007;11:383- 392.
58. Bazan NG, Lukiw WJ: Cyclooxygenase-2 and prese-nilin-1 gene expression induced by interleukin-1β and amyloid β42 peptide is potentiated by hypoxia in primary human neural cells. J Biol Chem 2002;277:30359-30367.
59. Bazan NG: Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 2003;44:2221-2233.
60. Bazan NG: Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends Neurosci 2006;29:263-271.
61. Bazan NG: Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care 2007;10:136-141.
62. Lahiri DK, Chen D, Vivien D, Ge Y W, Greig NH: Role of cytokines in the gene expression of amyloid β-protein precursor: identification of a 5'-UTR-binding nuclear factor and its implications in Alzheimer's disease. J Alzheimers Dis 2003;5:81- 90.
63. Stiehl DP, Jelkmann W, Wenger RH, Hellwig-Burgel T: Normoxic induction of the hypoxia-inducible factor 1α by insulin and interleukin-1β involves the phosphatidylinositol 3-kinase pathway. FEBS Lett 2002;512:157-162.
64. Sun GY, Xu J, Jensen MD, Simonyi A: Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J Lipid Res 2004;45:205- 213.
65. Poon HF, Calabrese V, Scapagnini G, Butterfield DA: Free radicals: key to brain aging and heme oxy-genase as a cellular response to oxidative stress. J Gerontol Biol Sci Med Sci 2004;59:478-493.
66. Barnham KJ, Masters CL, Bush AI: Neuro degenerative diseases and oxidative stress. Nat Rev Drug Discov 2004;3:205-214.
67. Kim H-Y, Akbar M, Lau A, Edsall L: Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6, n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 2000;275:35215-35223.
68. Cole GM, Frautschy SA: Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health 2006; 18:249-259.
69. Kim YJ, Chung HY: Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosa-pentaenoic acid in renal epithelial cells and macrophages. J Med Food 2007;10:225-231.
70. Pfrommer CA, Erl W, Weber PC: Docosahexaenoic acid induces ciap1 mRNA and protects human endothelial cells from stress-induced apoptosis. Am J Physiol Heart Circ Physiol 2006;290: H2178- H2186.
71. Qin W, Ho L, Pompl PN, Peng Y, Zhao Z, Xiang Z, Robakis NK, Shioi J, Suh J, Pasinetti GM: Cyclooxygenase (COX)-2 and COX-1 potentiate β-amyloid peptide generation through mechanisms that involve γ-secretase activity. J Biol Chem 2003;278:50970-50977.
72. Fujiwara Y, Yokoyama M, Sawada R, Seyama Y, Ishii M, Tsutsumi S, Aburatani H, Hanaka S, Itakura H, Matsumoto A: Analysis of the comprehensive effects of polyunsaturated fatty acid on mRNA expression using a gene chip. J Nutr Sci Vitaminol (Tokyo) 2003;49:125-132.
73. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG: Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA 2004;101:8491-8496.
74. Mukherjee PK, Marcheselli VL, Barreiro S, Hu J, Bok D, Bazan NG: Neurotrophins enhance retinal pigment epithelial cell survival through neuropro-tectin D1 signaling. Proc Natl Acad Sci USA 2007;104:13152-13157.
75. Mukherjee PK, Marcheselli VL, de Rivero Vaccari JC, Gordon WC, Jackson FE, Bazan NG: Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuro-protectin D1 synthesis. Proc Natl Acad Sci USA 2007; 104:13158-13163.
76. Chapkin RS, Davidson LD, Davidson LA: Phospholipid molecular species composition of mouse liver nuclei. Influence of dietary n-3 fatty acid ethyl esters. Biochem J 1992;287:237-240.
77. Lau FC, Shukitt-Hale B, Joseph JA: Nutritional intervention in brain aging: reducing the effects of inflammation and oxidative stress. Subcell Biochem 2007;42:299-318.
78. Puskas LG, Kitajka K, Nyakas C, Barcelo-Coblijn G, Farkas T: Short-term administration of omega-3 fatty acids from fish oil results in increased tran-sthyretin transcription in old rat hippocampus. Proc Natl Acad Sci USA 2003;100:1580-1585.
79. Kielar ML, Jeyarajah DR, Penfield JG, Lu CY: Docosahexaenoic acid decreases IRF-1 mRNA and thus inhibits activation of both the IRF-E and NF-κD response elements of the iNOS promoter. Transplantation 2000;69:2131-2137.
80. Lukiw WJ, Pelaez R P, Martinez J, Bazan NG: Budesonide epimer R or dexamethasone selectively inhibit platelet-activating factor-induced or inter-leukin- 1β-induced DNA binding activity of cis-acting transcription factors and cyclooxygenase-2 gene expression in human epidermal keratinocytes. Proc Natl Acad Sci USA 1998;95: 3914-3919.
81. Lukiw WJ, LeBlanc HJ, Carver LA, McLachlan DRC, Bazan NG: Run on transcription in human neocortical nuclei. J Mol Neurosci 1998;11:67-78.
82. Lukiw WJ, Rogaev EI, Bazan NG: Potential of tran-scriptional coordination of nine genes associated with Alzheimer's disease. Alzheimer Rep 2000;3: 231-242.
83. Lukiw WJ, Gordon WC, Rogaev EI, Thompson H, Bazan NG: Presenilin-2 expression up-regulation in a model of retinopathy of prematurity and pathoan-giogenesis. Neuroreport 2001;12:53-57.
84. Lukiw WJ, Ottlecz A, Lambrou G, Grueninger M, Finley J, Thompson H W, Bazan NG: Coordinate activation of HIF-1 and NF-κB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia. Invest Ophthalmol Vis Sci 2003;44:4163- 4170.
85. Rojas C V, Martinez JI, Flores I, Hoffman DR, Uauy R: Gene expression analysis in human fetal retinal explants treated with docosahexaenoic acid. Invest Ophthalmol Vis Sci 2003;44:3170-3177.
86. Roberts LJ 2nd, Montine TJ, Markesbery WR, Tapper AR, Hardy P, Chemtob S, Dettbarn WD, Morrow JD: Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosa-hexaenoic acid. J Biol Chem 1998;273: 13605-13612.
87. Roberts LJ 2nd, Fessel J P, Davies SS: The biochemistry of the isoprostane, neuroprostane, and isofuran pathways of lipid peroxidation. Brain Pathol 2005; 15:143-148.
88. Zhao Y, Cui JG, Lukiw WJ: Reduction of sortilin-1 in Alzheimer hippocampus and in cytokine-stressed human brain cells. Neuroreport 2007;18:1187- 1191.
89. Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, Hardy M, Gimenez JM, Chiang N, Serhan CN, Bazan NG: Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003;278:43807-43817.
90. Scott BL, Bazan NG: Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc Natl Acad Sci USA 1989;86:2903-2907.
91. Van Broeck B, Van Broeckhoven C, Kumar-Singh S: Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches. Neurodegener Dis 2007;4:349- 365.
92. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes, J P, van Belle G, Berg L: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of AD. Neurology 1991;41:479-486.
93. Casserly I, Topol E: Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet 2004;363:1139- 1146.
94. Shie FS, LeBoeur RC, Jin LW: Early intraneuronal Aβ deposition in the hippocampus of APP trans-genic mice. Neuroreport 2003;14:123-129.
95. Guo Q, Sopher BL, Furukawa K, Pham DG, Robinson N, Martin GM, Mattson MP: Alzheimer's presenilin mutation sensitizes neural cells to apop-tosis induced by trophic factor withdrawal and amyloid β-peptide: involvement of calcium and oxyradicals. J Neurosci 1997;17:4212-422.
96. Guo Q, Robinson N, Mattson MP: Secreted β-amyloid precursor protein counteracts the proapoptotic action of mutant presenilin-1 by activation of NF-κB and stabilization of calcium homeostasis. J Biol Chem 1998;273:12341-12351.
97. Lukiw WJ: Cholesterol and 24S-hydroxycholesterol trafficking in Alzheimer's disease. Expert Rev Neurother 2006;6:683-693.
98. Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, Broersen L, Lutjohann D, Hartmann T, Tanila H: Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on β-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis 2006;23:563-572.
99. Green KN, Martinez-Coria H, Khashwji H, Hall EB, Yurko-Mauro KA, Ellis L, LaFerla FM: Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-β and τ pathology via a mechanism involving presenilin 1 levels. J Neurosci 2007; 27:4385-4395.
100. Tansley GH, Burgess BL, Bryan MT, Su Y, Hirsch-Reinshagen V, Pearce J, Chan JY, Wilkinson A, Evans J, Naus KE, McIsaac S, Bromley K, Song W, Yang HC, Wang N, DeMattos RB, Wellington CL: The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of β-amyloid precursor protein. J Lipid Res 2007; 48:1022-1034.
101. Cheng H, Vetrivel KS, Gong P, Meckler X, Parent A, Thinakaran G: Mechanisms of disease: new therapeutic strategies for Alzheimer's disease-targeting APP processing in lipid rafts. Nat Clin Pract Neurol 2007;3:374-382.
102. Hirsch-Reinshagen V, Wellington CL: Cholesterol metabolism, apolipoprotein E, adenosine triphos-phate-binding cassette transporters, and Alzheimer's disease. Curr Opin Lipidol 2007;18:325-332.
103. Grimm MO, Grimm HS, Hartmann T: Amyloid β as a regulator of lipid homeostasis. Trends Mol Med 2007;13:337-344.
104. Zinser EG, Hartmann T, Grimm MO: Amyloid β-protein and lipid metabolism. Biochim Biophys Acta 2007;1768:1991-2001.
105. Wirths O, Thelen KM, Lutjohann D, Falkai P, Bayer TA: Altered cholesterol metabolism in APP695-transfected neuroblastoma cells. Brain Res 2007; 1152:209-214.
106. Grimm MO, Tschape JA, Grimm HS, Zinser EG, Hartmann T: Altered membrane fluidity and lipid raft composition in presenilin-deficient cells. Acta Neurol Scand Suppl 2006;185:27-32.
107. Sahlin C, Pettersson FE, Nilsson LN, Lannfelt L, Johansson AS: Docosahexaenoic acid stimulates non-amyloidogenic APP processing resulting in reduced Aβ levels in cellular models of Alzheimer's disease. Eur J Neurosci 2007;26:882-889.
108. Wolozin B: Cholesterol and the biology of Alzheimer's disease. Neuron 2004;41:7-10.
109. Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T: Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo. Proc Natl Acad Sci USA 2001;98:5856-5861.
110. Cordy JM, Hooper NM, Turner AJ: The involvement of lipid rafts in Alzheimer's disease. Mol Membr Biol 2006;23:111-122.
111. Gamerdinger M, Clement AB, Behl C: Cholesterollike effects of selective cyclooxygenase inhibitors and fibrates on cellular membranes and amyloid-β production. Mol Pharmacol 2007;72:141-151.
112. Carter CJ: Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis. Neurochem Int 2007;50:12-38.
113. Famer D, Meaney S, Mousavi M, Nordberg A, Bjorkhem I, Crisby M: Regulation of α- and β-secretase activity by oxysterols: cerebrosterol stimulates processing of APP via the α-secretase pathway. Biochem Biophys Res Commun 2007; 359:46-50.
114. Kim WS, Rahmanto AS, Kamili A, Rye KA, Guillemin GJ, Gelissen IC, Jessup W, Hill AF, Garner B: Role of ABCG1 and ABCA1 in regulation of neu-ronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-β peptide generation. J Biol Chem 2007;282:2851-2861.
115. Thinakaran G: Metabolism of presenilins. J Mol Neurosci 2001;17:183-192.
116. Murphy M P, Das P, Nyborg AC, Rochette MJ, Dodson MW, Loosbrock NM, Souder TM, McLendon C, Merit SL, Piper SC, Jansen KR, Golde TE: Overexpression of nicastrin increases Aβ production. FASEB J 2003;17:1138-1140.
117. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR: Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ-secretase. Hum Mol Genet 2004;13:159-170.
118. Tong L, Thornton PL, Balazs R, Cotman CW: Beat-amyloid-(1-42) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival Is not compromised. J Biol Chem 2001;276:17301- 17306.
119. Turner RS, Suzuki N, Chyung AS, Younkin SG, Lee VM: Amyloids β40 and β42 are generated intracel-lularly in cultured human neurons and their secretion increases with maturation. J Biol Chem 1996; 271:8966-8970.
120. Barger SW, Mattson MP: Participation of gene expression in the protection against amyloid β-peptide toxicity by the β-amyloid precursor protein. Ann NY Acad Sci 1996;777:303-309.
121. Gordon WC, Bazan NG: Docosahexaenoic acid utilization during rod photoreceptor cell renewal. J Neurosci 1990;10:2190-2202.
122. Gamoh S, Hashimoto M, Sugioka K, Shahdat Hossain M, Hata N, Misawa Y, Masumura S: Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 1999;93:237-241.
123. Girouard H, Iadecola C: Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 2006;100:328- 335.
124. Colangelo V, Schurr J, Ball MJ, Pelaez R P, Bazan NG, Lukiw WJ: Gene expression profiling of 12,633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 2002;70:462-473.
125. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP: Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci USA 2004;101:2070-2075.
126. Grant WB: Dietary links to Alzheimer's Disease: 1999 update. J Alzheimers Dis 1999;1:197-201.
127. Vaya J, Schipper HM: Oxysterols, cholesterol homeostasis, and Alzheimer disease. J Neurochem 2007;102:1727-1737.
128. Fukumoto H, Rosene DL, Moss MB, Raju S, Hyman BT, Irizarry MC: Beta-secretase activity increases with aging in human, monkey, and mouse brain. Am J Pathol 2004;164:719-725.
129. Flood DG, Reaume AG, Dorfman KS, Lin YG, Lang DM, Trusko SP, Savage MJ, Annaert WG, De Strooper B, Siman R, Scott RW: FAD mutant PS-1 gene-targeted mice: increased Aβ, 42 and Aβ deposition without APP overproduction. Neurobiol Aging 2002;23:335-348.
130. Cui JG, Kuroda H, Chandrasekharan NV, Pelaez RP, Dimmons DL, Bazan NG, Lukiw WJ: Cyclo-oxygenase-3 gene expression in Alzheimer hippocampus and in stressed human neural cells. Neurochem Res 2004;29:1731-1737.
131. Tarte K, Jourdan M, Veyrune JL, Berberich I, Fiol G, Redal N, Shaughnessy J, Klein B: The Bcl-2 family member Bfl-1/A1 is strongly repressed in normal and malignant plasma cells but is a potent anti-apoptotic factor for myeloma cells. Br J Haematol 2004;125:373-382.
132. Akhtar RS, Ness JM, Roth KA: Bcl-2 family regulation of neuronal development and neurodegenera-tion. Biochim Biophys Acta 2004;1644:189-203.
133. Metcalfe AD, Hunter HR, Bloor DJ, Lieberman BA, Picton HM, Leese HJ, Kimber SJ, Brison DR: Expression of 11 members of the Bcl-2 family of apoptosis regulatory molecules during human pre-implantation embryo development and fragmentation. Mol Reprod Dev 2004;68:35-50.
134. Serhan CN, Clish CB, Brannon J, Colgan S, Chiang N, Gronert K: Anti-microinflammatory lipid signals generated from dietary n-3 fatty acids via cyclooxy-genase-2 and transcellular processing: a novel mechanism for NSAID and n-3 PUFA therapeutic actions. J Exp Med 2000;192:1197-1204.
135. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL: Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002;196:1025-1037.
136. Graham SH, Chen J, Clark RS. Bcl-2 family gene products in cerebral ischemia and traumatic brain injury. J Neurotrauma 2000;17:831-841.
137. Markesbery WR, Kryscio RJ, Lovell MA, Morrow JD: Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment. Ann Neurol 2005;58:730-735.
138. Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM: The role of cholesterol in the biosynthesis of β-amyloid. Neuroreport 1999;10:1699-1705.
139. Schenk D: Alzheimer's disease: a partner for prese-nilin. Nature 2002;407:48-54.
140. Takeda K, Araki W, Tabira T: Enhanced generation of intracellular Aβ42 amyloid peptide by mutation of presenilins PS1 and PS2. Eur J Neurosci 2004;19: 258-264.
141. Mattson M P, Mattson EP: Amyloid peptide enhances nail rusting: novel insight into mechanisms of aging and Alzheimer's disease. Ageing Res Rev 2002;1: 327-330.
142. Stein TD, Johnson JA: Genetic programming by the proteolytic fragments of the amyloid precursor protein: somewhere between confusion and clarity. Rev Neurosci 2003;14:317-341.
143. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 1998;95:6460-6464.
144. Notkola IL, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, Tuomilehto J, Nissinen A: Serum total cholesterol, apolipoprotein E ε4 allele, and Alzheimer's disease. Neuroepidemiology 1998;17:14-20.
145. Webster NJ, Green KN, Peers C, Vaughan PF: Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia. J Neurochem 2002;83:1262-1271.
146. Bodovitz S, Klein WL: Cholesterol modulates α-secretase cleavage of amyloid precursor protein. J Biol Chem 1996;271:4436-4440.
147. 2 activity in the neurites/nerve growth cones of PC12 cells. J Neurosci Res 1998;54:805- 813.
148. Meyer BJ, Hammervold T, Rustan AC, Howe PR: Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects. Lipids 2007;42:109-115.