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研究生:藍文安
研究生(外文):Wen-Ann Lan
論文名稱:類澱粉蛋白-beta誘導阿茲海默症大鼠不同組織內生性反式脂肪含量之分析
論文名稱(外文):Analysis of endogenous trans-fatty acids in different tissues of beta amyloid peptide induced Alzheimer’s disease Sprague-Dawley rats
指導教授:孫璐西孫璐西引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:食品科技研究所
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:112
中文關鍵詞:阿茲海默症類澱粉蛋白 (-beta)內生性反式脂肪自由基S-D大鼠氣相層析串連質譜儀
外文關鍵詞:beta-amyloid peptideendogenous trans fatty acidsfree radicalsS-D ratsgas chromatography-mass spectrometry
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反式脂肪酸(Trans fatty acids, TFAs)為包含一或多個不共軛反式雙鍵結構之不飽和脂肪酸,其主要來源為加工食品中部分氫化的油脂,1990年代許多研究均指出攝取過多反式脂肪會升高罹患心血管疾病的風險。
近年的研究指出體內反式脂肪除食物來源之外,尚有部分經自由基誘導脂肪酸順反異構化之反式脂肪酸在體內生成,即內生性 (endogenous)反式脂肪,其生成量與體內自由基含量呈正相關。研究中指出吸煙者、誘導發炎大鼠及正常老化的大鼠體內具有較多內生性反式脂肪。阿茲海默症 (Alzheimer''s disease, AD)為目前失智症最主要的一類,患者腦部出現含有類澱粉蛋白(beta-amyloid peptide, Aβ)的老化斑塊沈積 (senile plaques)及神經糾結 (tangles),且在腦部可觀察到升高的氧化壓力及發炎反應,推測較高之氧化壓力及發炎亦可能引起脂肪酸順反式異構化。本研究乃探討側腦室注射Aβ25-35誘導阿茲海默症之Sprague-Dawley 大鼠 (SD rats)的腦部、肝臟、心臟及脂肪組織中是否有較高量內生性反式脂肪酸之存在,期可應用為AD之預測性指標。
本研究共分為兩部分,其一為分析大鼠組織內氧化壓力指標,另一部份為分析大鼠組織內脂肪酸組成。在氧化壓力指標方面,肝臟脂質過氧化物thiobarbituric acid reactive substances (TBARS)含量與肝臟麩胱甘肽還原酶 (glutathione reductase, GRd)活性分析中發現Aβ注射組之大鼠體內可能有偏高之氧化壓力。而在肝臟麩胱甘肽過氧化酶 (glutathione peroxidase, GPx)活性分析與血漿TBARS含量分析結果方面則無顯著差異。
在脂肪酸組成分析方面,使用氣相層析串聯質譜儀分析生理食鹽水注射組 (控制組)、Aβ注射組與Aβ及resveratrol 同時注射組之大鼠腦部、肝臟、腹部脂肪組織、副睪脂肪組織與皮下脂肪組織之脂肪酸組成時,發現各組皆未檢出反式脂肪酸,或其含量低於偵測下限,僅大鼠心臟組織中有檢出低於定量極限之反式脂肪,而各組之主要脂肪酸組成則無顯著差異。但Aβ組大鼠腹部脂肪總脂肪酸含量則顯著低於控制組;而Aβ及resveratrol 同時注射組大鼠腹部脂肪總脂肪酸含量亦低於控制組。未偵測到反式脂肪的原因推測如後,注射Aβ之劑量及時間所引致之自由基不足以導致內生性反式脂肪酸生成,或因注射Aβ而生成的自由基侷限在腦內小部分區域 (如海馬迴),或是採集組織的時間已超過發炎的急性期而自由基生成量減少。未來可進一步探討AD導致自由基生成量之測定與其造成內生性反式脂肪生成的能力。
綜合上述結果,由側腦室連續7天注射Aβ25-35誘發AD之大鼠的腦部、肝臟與脂肪組織中並未偵測到內生性反式脂肪,僅在各組的心臟組織內則偵測到微量TFAs,且各組織中之脂肪酸組成與控制組比較並無顯著差異。


Trans fatty acids (TFAs) are defined as “unsaturated fatty acids that contain one or more isolated (i.e., nonconjugated) double bonds in a trans configuration.”TFAs mainly come from partial hydrogenated oil in processed foods and investigations of TFAs in the 90’s indicated that over intake of TFAs may increase the risk of cardiovascular diseases.
Besides from foods, TFAs may also be formed by free radical induced cis/trans isomerization of endogenous fatty acids from recent investigations and the formation of the “endogenous TFAs” was positively related with the amount of free radicals. Higher levels of endogenous TFAs were found in the smokers, lipopolysaccharides (LPS)-induced inflammation rats and normal aged rats. Alzheimer''s disease (AD) is the main cause of dementia. The senile plaques with beta-amyloid peptide (Aβ) and the neuron tangles are universal pathological characters of AD brain . We suspected that the higher oxidative stress and inflammation in AD brain might induce cis/trans isomerization of fatty acids. The objective of this study is to investigate if there are more endogenous TFAs in brains, livers and adipose tissues of ventriclely injected Aβ25-35 induced AD rats, and we hope that the endogenous TFAs can be an indicator of AD.
The study was divided into two parts. The first part was to analyze the oxidative biomarkers, and the second part was to analyze the fatty acid compositions of brains, livers, hearts and adipose tissues. In the oxidative biomarker analyses, liver TBARS and liver glutathione reductase (GRd) activities showed that oxidative stress may be higher in Aβ25-35 group, while plasma TBARS and glutathione peroxidase (GPx) activities were similar in all five groups.
We also analyzed fatty acid compositions of brains, livers, hearts, abdominal adipose tissue, epidydimal adipose tissue and subcutaneous adipose tissue from rats of saline (control), Aβ and ‘Aβwith resveratrol’ injection group. No TFAs were detected and fatty acid compositions were not significantly different in brains, livers, and adipose tissues from the three groups, while trace TFAs (lower than the limit of quantification)were detected in hearts. Besides, total fatty acids content in abdominal adipose tissue from Aβand Aβ with resveratrol’groups were significantly lower than the control group. We infer that the absence of endogenous TFAs might due to not sufficient free radicals induced during seven days of Aβ25-35 injection, or Aβ induced free radicals concentrated only in limited area in brain (such as hippocampus), or even the sacrifice time point was after the acute inflammation period and resulted in decreased free radicals. In the future study, we suggest to investigate the amount of free radicals induced during AD and its ability to promote the formation of endogenous TFAs.
In conclusion, no detectable levels of endogenous TFAs were found in brains, livers and adipose tissues or only trace amount of TFAs appeared in hearts from ventricle injection of Aβ25-35 induced AD rats, and the fatty acid compositions were not significantly different from the control group.


論文口試委員審定書
誌謝 I
中文摘要 II
英文摘要 IV
目錄 VI
圖目錄 X
表目錄 XII
縮寫表 XIV
壹、 前言 1
貳、 文獻整理 3
一、 脂肪酸 3
(一) 飽和脂肪酸 3
(二) 不飽和脂肪酸 4
二、 反式脂肪酸 6
(一) 反式脂肪酸定義 6
(二) 反式脂肪與營養 8
(三) 反式脂肪酸的物理化學特性 8
(四) 反式脂肪與心血管疾病 9
(五) TFAs與糖尿病 11
三、 非食物來源反式脂肪酸 12
(一) 原核生物對環境壓力的調節 12
(二) 自由基催化順反異構化反應 12
四、 內生性反式脂肪酸 13
(一) 硫氫自由基導致內生性反式脂肪 13
(二) 氮氧自由基導致內生性反式脂肪 14
五、 反式花生四烯酸 (TAA)之來源與生理影響 16
(一) TAA之來源 16
(二) 發炎 18
(三) 吸煙 18
(四) 微血管擴張 19
(五) 微血管內皮細胞凋亡 (Apoptosis) 19
(六) 視網膜病變 19
(七) 血小板 20
六、 阿茲海默症 20
(一) 阿茲海默症盛行率 20
(二) 阿茲海默症症狀 21
(三) 阿茲海默症致病機制 21
(四) 阿茲海默症成因 22
(五) 阿茲海默症與氧化壓力 22
七、 阿茲海默症齧齒類動物模式 23
(一) 自發性的模式 23
(二) 藥理學、化學或手術切除模式 24
八、 動物組織脂肪萃取方法 26
(一) Folch 方法 26
(二) Bligh and Dyer 法 26
九、 脂質衍生化方法 27
(一) 加熱協助水解與酯化 27
(二) 酸催化 27
(三) 鹼催化 28
十、 脂肪酸定量與定性方法 28
(一) 傅立葉轉換紅外光譜法 29
(二) 高效液相層析法 29
(三) 氣相層析法 30
十一、 白藜蘆醇 (Resveratrol ) 32
參、 研究目的與實驗架構 33
一、 研究目的 33
二、 實驗架構 34
肆、 材料與方法 35
一、 實驗材料 35
(一) 實驗動物組織 35
(二) 試劑與試藥 36
(三) 緩衝溶液配置 39
(四) 儀器設備 39
(五) 分析儀器 40
二、 實驗方法 41
(一) TBARS 41
(二) 麩胱甘肽過氧化酶 (Glutathione peroxidase, GPx)活性分析 42
(三) 麩胱甘肽還原酶 (Glutathione reductase, GRd)活性分析 42
(四) 組織脂肪酸定量 42
三、 統計方法 49
伍、 結果與討論 50
一、 生化分析 50
(一) TBARS 50
(二) GRd酵素活性分析 54
(三) GPx酵素活性分析 56
二、 脂肪酸分析 58
(一) 分析條件及分離效果評估方法 58
(二) 精密度分析結果 62
(三) 偵測極限與定量極限 62
(四) 標準曲線繪製 63
(五) 酯化率 67
三、 大鼠組織脂肪酸組成分析 68
(一) 腦部 68
(二) 肝臟 72
(三) 心臟 76
(四) 腹部脂肪組織 80
(五) 副睪脂肪組織 84
(六) 皮下脂肪組織 88
陸、 結論 91
柒、 未來研究 92
捌、 參考文獻 93
玖、 附錄 102
一、 肝臟酵素活性分析與TBARS 102
二、 脂肪酸甲基酯轉換為脂肪酸及三酸甘油酯之係數 103
三、 各組織中粗脂肪及甲基酯重量統計表 103
四、 選定離子片段質譜掃瞄 (SIM)腦部、肝臟及心臟FAME 106
五、 實驗大鼠飼料成分 111



Adlof, R.; Copes, L.; Emken, E. Analysis of the monoenoic fatty acid distribution in hydrogenated vegetable oils by silver-ion high-performance liquid chromatography. J. Am. Oil Chem. Soc. 1995, 72, 571-574.
Adlof, R. O. Analysis of fatty acid mono- and diacylglycerol positional isomers by silver ion high-performance liquid chromatography. Journal of Chromatography A 1996, 741, 135-138.
Antolín, E. M.; Delange, D. M.; Canavaciolo, V. G. Evaluation of five methods for derivatization and gc determination of a mixture of very long chain fatty acids (c24:0-c36:0). J. Pharm. Biomed. Anal. 2008, 46, 194-199.
Asperger, A.; Engewald, W.; Fabian, G. Thermally assisted hydrolysis and methylation - a simple and rapid online derivatization method for the gas chromatographic analysis of natural waxes. J. Anal. Appl. Pyrolysis 2001, 61, 91-109.
Axen, K. V.; Dikeakos, A.; Sclafani, A. High dietary fat promotes syndrome x in nonobese rats. J. Nutr. 2003, 133, 2244-2249.
Balazy, M. In Trans-arachidonic acids: New mediators of inflammation, 2000; J Physiol Pharmacol: 2000; pp 597-607.
Balazy, M.; Chemtob, S. Trans-arachidonic acids: New mediators of nitro-oxidative stress. Pharmacol. Ther. 2008, 119, 275-290.
Balazy, M.; Iesaki, T.; Park, J. L.; Jiang, H.; Kaminski, P. M.; Wolin, M. S. Vicinal nitrohydroxyeicosatrienoic acids: Vasodilator lipids formed by reaction of nitrogen dioxide with arachidonic acid. J. Pharmacol. Exp. Ther. 2001, 299, 611-619.
Balazy, M.; Poff, C. D. Biological nitration of arachidonic acid. Curr. Vasc. Pharm. 2004, 2, 81-93.
Bellomo, G.; Mirabelli, F.; Dimonte, D.; Richelmi, P.; Thor, H.; Orrenius, C.; Orrenius, S. Formation and reduction of glutathione-protein mixed disulfides during oxidative stress - a study with isolated hepatocytes and menadione (2-methyl-1,4-naphthoquinone). Biochem. Pharmacol. 1987, 36, 1313-1320.
Bligh, E. G.; Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959, 37, 911-917.
Brondz, I. Development of fatty acid analysis by high-performance liquid chromatography, gas chromatography, and related techniques. Anal. Chim. Acta 2002, 465, 1-37.
Bruhl, L. Determination of trans fatty acids in cold pressed oils and in dried seeds. Fett-Lipid 1996, 98, 380-383.
Bush, A. I.; Masters, C. L.; Tanzi, R. E. Copper, beta-amyloid, and alzheimer''s disease: Tapping a sensitive connection. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 11193-11194.
Butterfield, D. A.; Drake, J.; Pocernich, C.; Castegna, A. Evidence of oxidative damage in alzheimer''s disease brain: Central role for amyloid beta-peptide. Trends Mol. Med 2001, 7, 548-554.
Butterfield, D. A.; Poon, H. F. The senescence-accelerated prone mouse (samp8): A model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in alzheimer''s disease. Exp. Gerontol. 2005, 40, 774-783.
Challinor, J. M. A pyrolysis-derivatisation-gas chromatography technique for the structural elucidation of some synthetic polymers. J. Anal. Appl. Pyrolysis 1989, 16, 323-333.
Chatgilialoglu, C.; Ferreri, C.; Ballestri, M.; Mulazzani, Q. G.; Landi, L. Cis−trans isomerization of monounsaturated fatty acid residues in phospholipids by thiyl radicals. J. Am. Chem. Soc. 2000, 122, 4593-4601.
Christie, W. W.; Sebedio, J. L.; Perkins, E. G., New trends in lipid and lipoprotein analyses. AOCS Press: Champaign, IL,, 1995.
Delmonte, P.; Kramer, J. K. G.; Yurawecz, M. P.; Mossoba, M. M.; Brena, J. T.; McDonald, R. E., Lipid analysis and lipodomics: New techniques and applications,. AOCS Press: Champaign, IL, 2006.
Dijkstra, A. J.; Hamilton, R. J.; Hamm, W., Trans fatty acids. Blackwell Publishing Ltd.: Oxford, UK, 2008.
Eras, J.; Montañes, F.; Ferran, J.; Canela, R. Chlorotrimethylsilane as a reagent for gas chromatographic analysis of fats and oils. Journal of Chromatography A 2001, 918, 227-232.
Erickson, C. A.; Barnes, C. A. The neurobiology of memory changes in normal aging. Exp. Gerontol. 2003, 38, 61-69.
Fabbri, D.; Baravelli, V.; Chiavari, G.; Prati, S. Dimethyl carbonate as a novel methylating reagent for fatty acids in analytical pyrolysis. Journal of Chromatography A 2005, 1065, 257-264.
Ferreri, C.; Angelini, F.; Chatgilialoglu, C.; Dellonte, S.; Moschese, V.; Rossi, P.; Chini, L. Trans fatty acids and atopic eczema/dermatitis syndrome: The relationship with a free radical cis-trans isomerization of membrane lipids. Lipids 2005a, 40, 661-667.
Ferreri, C.; Costantino, C.; Perrotta, L.; Landi, L.; Mulazzani, Q. G.; Chatgilialoglu, C. Cis-trans isomerization of polyunsaturated fatty acid residues in phospholipids catalyzed by thiyl radicals. J. Am. Chem. Soc. 2001, 123, 4459-4468.
Ferreri, C.; Kratzsch, S.; Brede, O.; Marciniak, B.; Chatgilialoglu, C. Trans lipid formation induced by thiols in human monocytic leukemia cells. Free Radic. Biol. Med. 2005b, 38, 1180-1187.
Ferreri, C.; Kratzsch, S.; Landi, L.; Brede, O. Thiyl radicals in biosystems: Effects on lipid structures and metabolisms. Cell. Mol. Life Sci. 2005c, 62, 834-847.
Ferri, C. P.; Prince, M.; Brayne, C.; Brodaty, H.; Fratiglioni, L.; Ganguli, M.; Hall, K.; Hasegawa, K.; Hendrie, H.; Huang, Y.; Jorm, A.; Mathers, C.; Menezes, P. R.; Rimmer, E.; Scazufca, M. Global prevalence of dementia: A delphi consensus study. The Lancet 2005, 366, 2112-2117.
Folch, J.; Lees, M.; Stanley, G. H. S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957, 226, 497-509.
Götz, J.; Schild, A.; Hoerndli, F.; Pennanen, L. Amyloid-induced neurofibrillary tangle formation in alzheimer''s disease: Insight from transgenic mouse and tissue-culture models. International Journal of Developmental Neuroscience 2004, 22, 453-465.
Golay, P.-A.; Dionisi, F.; Hug, B.; Giuffrida, F.; Destaillats, F. Direct quantification of fatty acids in dairy powders with special emphasis on trans fatty acid content. Food Chem. 2007, 101, 1115-1120.
Haass, C.; Lemere, C. A.; Capell, A.; Citron, M.; Seubert, P.; Schenk, D.; Lannfelt, L.; Selkoe, D. J. The swedish mutation causes early-onset alzheimer''s disease by [beta]-secretase cleavage within the secretory pathway. Nat Med 1995, 1, 1291-1296.
Han, S. N.; Leka, L. S.; Lichtenstein, A. H.; Ausman, L. M.; Schaefer, E. J.; Meydani, S. N. Effect of hydrogenated and saturated, relative to polyunsaturated, fat on immune and inflammatory responses of adults with moderate hypercholesterolemia. J. Lipid Res. 2002, 43, 445-452.
Hardell, H.-L.; Nilvebrant, N.-O. A rapid method to discriminate between free and esterified fatty acids by pyrolytic methylation using tetramethylammonium acetate or hydroxide. J. Anal. Appl. Pyrolysis 1999, 52, 1-14.
Hardy, J. Amyloid, the presenilins and alzheimer''s disease. Trends in Neurosciences 1997, 20, 154-159.
Harkany, T.; Ábrahám, I.; Timmerman, W.; Laskay, G.; Tóth, B.; Sasvári, M.; Kónya, C.; Sebens, J. B.; Korf, J.; Nyakas, C.; Zarándi, M.; Soós, K.; Penke, B.; Luiten, P. G. M. Amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis. Eur. J. Neurosci. 2000, 12, 2735-2745.
Harkany, T.; O''Mahony, S.; Kelly, J. P.; Soós, K.; Törõ, I.; Penke, B.; Luiten, P. G. M.; Nyakas, C.; Gulya, K.; Leonard, B. E. [beta]-amyloid(phe(so3h)24)25-35 in rat nucleus basalis induces behavioral dysfunctions, impairs learning and memory and disrupts cortical cholinergic innervation. Behav. Brain Res. 1998, 90, 133-145.
Heipieper, H. J.; Meinhardt, F.; Segura, A. The cis-trans isomerase of unsaturated fatty acids in pseudomonas and vibrio : Biochemistry, molecular biology and physiological function of a unique stress adaptive mechanism. FEMS Microbiol. Lett. 2003, 229, 1-7.
Hsiao, K.; Chapman, P.; Nilsen, S.; Eckman, C.; Harigaya, Y.; Younkin, S.; Yang, F.; Cole, G. Correlative memory deficits, abeta elevation, and amyloid plaques in transgenic mice. Science 1996, 274, 99-103.
Huang, Z.; Wang, B.; Crenshaw, A. A. A simple method for the analysis of trans fatty acid with gc-ms and at(tm)-silar-90 capillary column. Food Chem. 2006, 98, 593-598.
Ibrahim, A.; Natarajan, S.; Ghafoorunissa. Dietary trans-fatty acids alter adipocyte plasma membrane fatty acid composition and insulin sensitivity in rats. Metabolism 2005, 54, 240-246.
Iverson, S.; Lang, S.; Cooper, M. Comparison of the bligh and dyer and folch methods for total lipid determination in a broad range of marine tissue. Lipids 2001, 36, 1283-1287.
Jan A. M. Smeitink; Rob C. A. Sengers; Trijbels, J. M. F., Oxidative phosphorylation in health and disease. Springer; 1 edition: 2005.
Jiang, H.; Kruger, N.; Lahiri, D. R.; Wang, D.; Vatèle, J.-M.; Balazy, M. Nitrogen dioxide inducescis-trans-isomerization of arachidonic acid within cellular phospholipids. J. Biol. Chem. 1999, 274, 16235-16241.
Jo, C.; Ahn, D. Fluorometric analysis of 2-thiobarbituric acid reactive substances in turkey. Poult. Sci. 1998, 77, 475-480.
Jun-Kai, D.; Wei, J.; Tian-Zhi, Z.; Ming, S.; Xiao-Guang, Y.; Chui-Chang, F. The effect of isomerization and degradation of polyunsaturated fatty acids from oils by different volume proportions of tetramethylammonium hydroxide in thermally assisted hydrolysis and methylation. J. Anal. Appl. Pyrolysis 1997, 42, 1-8.
Kermorvant-Duchemin, E.; Sennlaub, F.; Sirinyan, M.; Brault, S.; Andelfinger, G.; Kooli, A.; Germain, S.; Ong, H.; d''Orleans-Juste, P.; Gobeil, F.; Zhu, T.; Boisvert, C.; Hardy, P.; Jain, K.; Falck, J. R.; Balazy, M.; Chemtob, S. Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration. Nat. Med. 2005, 11, 1339-1345.
Khatsenko, O. G.; Gross, S. S.; Rifkind, A. B.; Vane, J. R. Nitric oxide is a mediator of the decrease in cytochrome p450-dependent metabolism caused by immunostimulants. Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 11147-11151.
Koletzko, B.; Decsi, T. Metabolic aspects of trans fatty acids. Clin. Nutr. 1997, 16, 229-237.
Kooli, A.; Kermorvant-Duchemin, E.; Sennlaub, F.; Bossolasco, M.; Hou, X.; Honoré, J.-C.; Dennery, P. A.; Sapieha, P.; Varma, D.; Lachapelle, P.; Zhu, T.; Tremblay, S.; Hardy, P.; Jain, K.; Balazy, M.; Chemtob, S. Trans-arachidonic acids induce a heme oxygenase-dependent vasorelaxation of cerebral microvasculature. Free Radic. Biol. Med. 2008, 44, 815-825.
Kramer, J.; Blackadar, C.; Zhou, J. Evaluation of two gc columns (60-m supelcowax 10 and 100-m cp sil 88) for analysis of milkfat with emphasis on cla, 18:1, 18:2 and 18:3 isomers, and short- and long-chain fa. Lipids 2002, 37, 823-835.
Lagrost, L. Differential effects of cis and trans fatty acid isomers, oleic and elaidic acids, on the cholesteryl ester transfer protein activity. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1992, 1124, 159-162.
Lawrence, R. A.; Burk, R. F. Glutathione peroxidase-activity in selenium-deficient rat-liver. Biochem. Biophys. Res. Commun. 1976, 71, 952-958.
Lemaitre, R. N.; Siscovick, D. S.; Raghunathan, T. E.; King, I.; Pearce, R. M.; Cobb, L. A. Cell membrane levels of trans fatty acids and the risk of primary cardiac arrest. Circulation 2000, 102, 4065.
Levy-Lahad, E.; Wasco, W.; Poorkaj, P.; Romano, D.; Oshima, J.; Pettingell, W.; Yu, C.; Jondro, P.; Schmidt, S.; Wang, K.; al., e. Candidate gene for the chromosome 1 familial alzheimer''s disease locus. Science 1995, 269, 973-977.
Lichtenstein, A. H.; Schwab, U. S. Relationship of dietary fat to glucose metabolism. Atherosclerosis 2000, 150, 227-243.
Liu, X.; Miller, M. J. S.; Joshi, M. S.; Thomas, D. D.; Lancaster, J. R. Accelerated reaction of nitric oxide with o2 within the hydrophobic interior of biological membranes. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 2175-2179.
Lundberg, J. O.; Weitzberg, E.; Gladwin, M. T. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 2008, 7, 156-167.
Mattson, M. P. Pathways towards and away from alzheimer''s disease. Nature 2004, 430, 631-639.
Mauger, J.-F.; Lichtenstein, A. H.; Ausman, L. M.; Jalbert, S. M.; Jauhiainen, M.; Ehnholm, C.; Lamarche, B. Effect of different forms of dietary hydrogenated fats on ldl particle size. Am J Clin Nutr 2003, 78, 370-375.
McGowan, E.; Eriksen, J.; Hutton, M. A decade of modeling alzheimer''s disease in transgenic mice. Trends Genet. 2006, 22, 281-289.
Mensink, R. P.; Katan, M. B. Trans monounsaturated fatty acids in nutrition and their impact on serum lipoprotein levels in man. Prog. Lipid Res. 1993, 32, 111-122.
Milinsk, M. C.; Matsushita, M.; Visentainer, J. V.; Oliveira, C. C. d.; Souza, N. E. d. Comparative analysis of eight esterification methods in the quantitative determination of vegetable oil fatty acid methyl esters (fame). J. Braz. Chem. Soc. 2008, 19, 1475-1483.
Morrison, W. R.; Smith, L. M. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride--methanol. J. Lipid Res. 1964, 5, 600-608.
Mossoba, M. M., Official methods for the determination of trans fat In AOCS Press: 2003.
Mossoba, M. M.; McDonald, R. E.; Prosser, A. R. Gas chromatographic/matrix isolation/fourier transform infrared spectroscopic determination of trans-monounsaturated and saturated fatty acid methyl esters in partially hydrogenated menhaden oil. J. Agric. Food Chem. 1993, 41, 1998-2002.
Murakami, Y.; Tsuyama, M.; Kobayashi, Y.; Kodama, H.; Iba, K. Trienoic fatty acids and plant tolerance of high temperature. Science 2000, 287, 476-479.
Nag, S.; Yee, B. K.; Tang, F. Reduction in somatostatin and substance p levels and choline acetyltransferase activity in the cortex and hippocampus of the rat after chronic intracerebroventricular infusion of [beta]-amyloid (1-40). Brain Res. Bull. 1999, 50, 251-262.
Nakamura, S.; Murayama, N.; Noshita, T.; Annoura, H.; Ohno, T. Progressive brain dysfunction following intracerebroventricular infusion of beta1-42-amyloid peptide. Brain Res. 2001, 912, 128-136.
Natarajan, S.; Ibrahim, A.; Ghafoorunissa. Dietary trans fatty acids alter diaphragm phospholipid fatty acid composition, triacylglycerol content and glucose transport in rats. [article]. British Journal of Nutrition June 2005, 93, 829-833.
Nikolova-Damyanova, B.; Christie, W. W., Advances in lipid methodology– one. The Oily Press: Ayr, Scotland, UK, 1992.
Oddo, S.; Caccamo, A.; Kitazawa, M.; Tseng, B. P.; LaFerla, F. M. Amyloid deposition precedes tangle formation in a triple transgenic model of alzheimer''s disease. Neurobiol. Aging 2003a, 24, 1063-1070.
Oddo, S.; Caccamo, A.; Shepherd, J. D.; Murphy, M. P.; Golde, T. E.; Kayed, R.; Metherate, R.; Mattson, M. P.; Akbari, Y.; LaFerla, F. M. Triple-transgenic model of alzheimer''s disease with plaques and tangles: Intracellular a[beta] and synaptic dysfunction. Neuron 2003b, 39, 409-421.
Odegaard, A. O.; Pereira, M. A. Trans fatty acids, insulin resistance, and type 2 diabetes. Nutrition Reviews 2006, 64, 364-372.
Oh, S.-H.; Ganther, H. E.; Hoekstra, W. G. Selenium as a component of glutathione peroxidase isolated from ovine erythrocytes. Biochemistry 1974, 13, 1825-1829.
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal-tissues by thiobarbituric acid reaction. Anal. Biochem. 1979, 95, 351-358.
Precht, D.; Molkentin, J. Rapid analysis of the isomers of trans-octadecenoic acid in milk fat. Int. Dairy J. 1996, 6, 791-809.
Pryor, W. A.; Houk, K. N.; Foote, C. S.; Fukuto, J. M.; Ignarro, L. J.; Squadrito, G. L.; Davies, K. J. A. Free radical biology and medicine: It''s a gas, man! Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006, 291, R491-511.
Ratnayake, W.; Gagnon, C.; Dumais, L.; Lillycrop, W.; Wong, L.; Meleta, M.; Calway, P. Trans fatty acid content of canadian margarines prior to mandatory trans fat labelling. J. Am. Oil Chem. Soc. 2007, 84, 817-825.
Ribé, E. M.; Pérez, M.; Puig, B.; Gich, I.; Lim, F.; Cuadrado, M.; Sesma, T.; Catena, S.; Sánchez, B.; Nieto, M.; Gómez-Ramos, P.; Morán, M. A.; Cabodevilla, F.; Samaranch, L.; Ortiz, L.; Pérez, A.; Ferrer, I.; Avila, J.; Gómez-Isla, T. Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant app/tau transgenic mice. Neurobiol. Dis. 2005, 20, 814-822.
Roses, A. D. A model for susceptibility polymorphisms for complex diseases: Apolipoprotein e and alzheimer disease. Neurogenetics 1997, 1, 3-11.
Ruiz-Gutiérrez, V.; Barron, L. J. R. Methods for the analysis of triacylglycerols. Journal of Chromatography B: Biomedical Sciences and Applications 1995, 671, 133-168.
Ruiz-Rodriguez, A.; Reglero, G.; Ibañez, E. Recent trends in the advanced analysis of bioactive fatty acids. J. Pharm. Biomed. Anal. 2010, 51, 305-326.
Salmeron, J.; Hu, F. B.; Manson, J. E.; Stampfer, M. J.; Colditz, G. A.; Rimm, E. B.; Willett, W. C. Dietary fat intake and risk of type 2 diabetes in women. Am J Clin Nutr 2001, 73, 1019-1026.
Scheuner, D.; Eckman, C.; Jensen, M.; Song, X.; Citron, M.; Suzuki, N.; Bird, T. D.; Hardy, J.; Hutton, M.; Kukull, W.; Larson, E.; Levy-Lahad, L.; Viitanen, M.; Peskind, E.; Poorkaj, P.; Schellenberg, G.; Tanzi, R.; Wasco, W.; Lannfelt, L.; Selkoe, D.; Younkin, S. Secreted amyloid [beta]-protein similar to that in the senile plaques of alzheimer''s disease is increased in vivo by the presenilin 1 and 2 and app mutations linked to familial alzheimer''s disease. Nat Med 1996, 2, 864-870.
Schwinn, H.; Sprinz, K.; Drossler, S.; Leistner, O.; Brede, J. Thiyl radical-induced cis/trans -isomerization of methyl linoleate in methanol and of linoleic acid residues in liposomes. International Journal of Radiation Biology 1998, 74, 359-365.
Selkoe, D. J.; Schenk, D. Alzheimer''s disease: Molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. 2003, 43, 545-584.
Shantha, N. C.; Napolitano, G. E. Gas chromatography of fatty acids. Journal of Chromatography A 1992, 624, 37-51.
Sherman, K. A.; Friedman, E. Pre- and post-synaptic cholinergic dysfunction in aged rodent brain regions: New findings and an interpretative review. International Journal of Developmental Neuroscience 1990, 8, 689-708.
Sherrington, R.; Rogaev, E. I.; Liang, Y.; Rogaeva, E. A.; Levesque, G.; Ikeda, M.; Chi, H.; Lin, C.; Li, G.; Holman, K.; Tsuda, T.; Mar, L.; Foncin, J. F.; Bruni, A. C.; Montesi, M. P.; Sorbi, S.; Rainero, I.; Pinessi, L.; Nee, L.; Chumakov, I.; Pollen, D.; Brookes, A.; Sanseau, P.; Polinsky, R. J.; Wasco, W.; Da Silva, H. A. R.; Haines, J. L.; Pericak-Vance, M. A.; Tanzi, R. E.; Roses, A. D.; Fraser, P. E.; Rommens, J. M.; St George-Hyslop, P. H. Cloning of a gene bearing missense mutations in early-onset familial alzheimer''s disease. Nature 1995, 375, 754-760.
Simopoulos, A. P. Summary of the nato advanced research workshop on dietary {omega}3 and {omega}6 fatty acids: Biological effects and nutritional essentiality. J. Nutr. 1989, 119, 521-528.
Smith, M. A.; Harris, P. L. R.; Sayre, L. M.; Perry, G. Iron accumulation in alzheimer disease is a source of redox-generated free radicals. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 9866-9868.
Sturchler-Pierrat, C.; Abramowski, D.; Duke, M.; Wiederhold, K.-H.; Mistl, C.; Rothacher, S.; Ledermann, B.; Bürki, K.; Frey, P.; Paganetti, P. A.; Waridel, C.; Calhoun, M. E.; Jucker, M.; Probst, A.; Staufenbiel, M.; Sommer, B. Two amyloid precursor protein transgenic mouse models with alzheimer disease-like pathology. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 13287-13292.
Tanzi, R. E.; Bertram, L. Alzheimer''s disease: The latest suspect. Nature 2008, 454, 706-708.
Toschi, T. G.; Capella, P.; Holt, C.; Christie, W. W. A comparison of silver ion hplc plus gc with fourier-transform ir spectroscopy for the determination of trans double bonds in unsaturated fatty acids. J. Sci. Food Agric. 1993, 61, 261-266.
Toyo''oka, T. Fluorescent tagging of physiologically important carboxylic acids, including fatty acids, for their detection in liquid chromatography. Anal. Chim. Acta 2002, 465, 111-130.
Van Dam, D.; De Deyn, P. P. Drug discovery in dementia: The role of rodent models. Nat Rev Drug Discov 2006, 5, 956-970.
W.W. Christie, Gas chromatography and lipids. Oil Press: Alloway, Scotland, 1989.
Ways, P.; Hanahan, D. J. Characterization and quantification of red cell lipids in normal man. J. Lipid Res. 1964, 5, 318-328.
Wolff, R.; Bayard, C. Improvement in the resolution of individualtrans-18:1 isomers by capillary gas-liquid chromatography: Use of a 100-m cp-sil 88 column. J. Am. Oil Chem. Soc. 1995, 72, 1197-1201.
Yamada, M.; Chiba, T.; Sasabe, J.; Nawa, M.; Tajima, H.; Niikura, T.; Terashita, K.; Aiso, S.; Kita, Y.; Matsuoka, M.; Nishimoto, I. Implanted cannula-mediated repetitive administration of a[beta]25-35 into the mouse cerebral ventricle effectively impairs spatial working memory. Behav. Brain Res. 2005, 164, 139-146.
Zambonin, L.; Prata, C.; Cabrini, L.; Maraldi, T.; Fiorentini, D.; Sega, F. V. D.; Hakim, G.; Landi, L. Effect of radical stress and ageing on the occurrence of trans fatty acids in rats fed a trans-free diet. Free Radic. Biol. Med. 2008, 44, 594-601.
Zghibeh, C. M.; Gopal, V. R.; Poff, C. D.; Falck, J. R.; Balazy, M. Determination of trans-arachidonic acid isomers in human blood plasma. Anal. Biochem. 2004, 332, 137-144.
Zock, P.; Katan, M.; Mensink, R. Dietary trans fatty acids and lipoprotein cholesterol. Am J Clin Nutr 1995, 61, 617-.


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