臺灣博碩士論文加值系統

高血糖、代謝症候群或第二型糖尿病、慢性酒精攝取等問題可能與神經退化疾病，例如認知功能異常或失智症等有著相關性，其機制可能包括有腦部神經細胞的能量代謝發生異常，以及血腦障壁的結構問題等。本研究第一部分以動物模式進行長期高果糖高脂肪飲食飼育誘發代謝性異常問題，包括高血糖及高血脂等，透過莫氏水迷宮評估認知功能，並分析腦部神經退化及訊息傳遞相關的蛋白質表現，之後以富含多元酚類物質的葡萄進行介入。結果發現高果糖高脂飲食導致認知功能、學習記憶能力等出現障礙，同時多種與神經退化相關的蛋白質表現出現異常。在以含有3%及6%葡萄冷凍乾燥粉末的高果糖高脂肪飲食進行為期12週的介入後，於實驗終點78週齡發現葡萄粉介入對於認知功能及相關蛋白質的表現均顯著較高果糖高脂飲食組別有所改善。此結果顯示長期高果糖高脂飲食至中高齡階段，可能誘發類似阿茲海默症的神經退化病變的病理表現，而葡萄的介入則具有緩解病變的形成及改善認知功能的效益。本研究第二部分以小鼠進行為期4週的慢性酒精攝入誘發模式，結果發現酒精攝入導致腦部氧化壓力、發炎指標及血腦障壁受損指標的表現上升，同時Brain-derived neurotrophic factor (BDNF) 下降。顯示腦部氧化壓力及發炎誘發神經退化，並且可能與血腦障壁受損有關。合併本研究兩部分結果顯示代謝疾病問題，包括血糖異常、氧化壓力提高等，與腦部的認知功能及神經退化病變形成有關，而葡萄的介入則具有緩解長期代謝異常所造成的神經退化問題的效益。

Abnormal glucose metabolism, metabolic disorder or Type 2 diabetes, or chronic alcohol consumption are associated with neurodegenerative diseases such as cognitive impairment or dementia. In the first part of this study, we investigated effects of diet induced metabolic disorder on cognitive function as well as the expression and/or phosphorylation of neurodegeneration-related brain proteins in rats fed high-fructose-high-fat (HFHF) diet. Wistar rats were given the HFHF diet for 53 weeks, followed by receving HFHF diet containing either 3% or 6% grape powder for additional 12 weeks. Results show that the inclusion of up to 6% grape powder in the HFHF diet resulted in better cognitive function and ameliorated the abnormal expression/hyperphosphorylation of neurodegeneration related proteins in the brain tissues of aged rats. In the second part of the study, a 4-week chronic alcohol consumption protocol was performed using mice model to evaluate the brain oxidative stress, inflammation and blood-brain barrier function. The results indicated alcohol consumption leaded to higher 8-hydroxy-2’-deoxyguanidine (8-OHdG) level, toll-like receptor-4 (TLR4) and matrix metallopeptidase 9 (MMP9) expressions; and lower level of brain-derived neurotrophy factor (BDNF). These results indicated alcohol consumption was associated with brain inflammatory response, oxidative stress and neurodegenerative phenomenon, and possibly a biood-brain barrier (BBB) dysfunction. In conclusion, chronic metabolic disorder leaded to increased oxidative stress in brain, cognitive impairment and neurodegeneration-related protein expression, and polyphenol-rich grape powder exhibited benefitial effects on the neurodegerative pathologenesis regression.

摘要 I
Abstract II
致謝 IV
目錄 V
圖目錄 VIII
表目錄 IX
第一章 文獻回顧 1
第一節 腦部神經退化性疾病的流行病學觀察 1
第二節 腦部的能量代謝狀態與認知功能 3
第三節 神經退化疾病問題與神經細胞的新陳代謝關聯性 6
第四節 神經退化病變的代謝相關效應 10
第五節 對葡萄糖代謝問題以天然食物成分介入可行性 11
第六節 血腦障壁在神經退化病變的角色 13
第七節 酒精誘發腦部病變的影響 15
第八節 酒精誘發模式 17
第二章 葡萄粉介入改善高果糖高脂飲食誘發之大鼠認知功能異常與神經退化 18
第一節 緒言 18
第二節 材料與方法 19
1. 實驗動物 19
2. 實驗設計 19
3. 介入飲食葡萄冷凍乾燥粉末製作 20
4. 莫氏水迷宮 (Morris Water Maze, MWM) 認知功能測試 20
5. 實驗期間血液檢體採集 22
6. 實驗終點動物犧牲及檢體收集 23
7. 血液檢體分析 23
8. 腦部蛋白質萃取及定量 24
9. 蛋白質電泳 24
10. 西方點墨法 24
11. 蛋白質分析標的 25
12. 組織糖化終產物分析 26
13. 統計分析 27
第三節 結果 28
1. 動物攝食量： 28
2. 實驗動物體重及血液生化數值 29
3. 莫氏水迷宮空間學習與記憶功能測試 30
4. 腦組織糖化終產物AGEs濃度 31
5. 腦組織RAGE蛋白質表現量 32
6. 腦組織Nrf2蛋白質表現量 33
7. 腦組織APP蛋白質表現量 34
8. 腦組織BACE蛋白質表現量 35
9. 腦組織Amyloid-beta (A) 蛋白質表現量 36
10. 腦組織的S396磷酸化Tau蛋白質與Tau蛋白質表現相對量 37
11. 腦組織的BDNF表現量 38
12. 腦組織的TrkB表現量 39
13. 腦組織的PI3K及磷酸化的PI3K (pPI3K) 表現量 40
14. 腦組織ERK 1/2及磷酸化的ERK 1/2 (pERK) 表現量 41
第四節 討論 42
1. 飲食誘發及介入模式 42
2. 血液生化指標 44
3. 高血糖與腦部的代謝及訊息傳遞路徑 45
4. 葡萄介入對HFHF誘發之認知功能異常及神經退化影響 47
5. 實驗介入正控制組Metformin的角色及活性 51
6. 本研究的強度及限制 53
第三章 小鼠慢性酒精攝入對於腦部氧化壓力及神經退化之探討 54
第一節 緒言 54
第二節 材料與方法 55
1. 實驗動物及實驗設計 55
2. 實驗終點動物犧牲及檢體採集 56
3. 血液樣本分析 56
4. 蛋白質萃取及定量 56
5. 蛋白質電泳 57
6. 西方點墨法 57
7. 蛋白質分析標的 57
8. 組織DNA氧化程度分析 58
9. 統計分析 59
第三節 結果 60
1. 實驗動物體重及攝食量 60
2. 血液生化檢測 61
3. 腦組織8-OHdG量 62
4. 腦組織MMP9蛋白質表現量 63
5. 腦組織TLR4蛋白質表現量 64
6. 腦組織GFAP蛋白質表現量 65
7. 腦組織BDNF表現量 66
第四節 討論 67
1. 酒精攝入的效應 67
2. 腦部的病變狀態 69
4. 本研究的限制 73
第四章 結論 74
參考文獻 75
附錄 117
一、 縮寫對照 117
二、 藥品配製 119
三、 高果糖高脂飲食誘發大鼠實驗模式動物實驗許可 122
四、 慢性酒精攝取誘發小鼠實驗模式動物實驗許可 123

Anstey, K. J., H. A. Mack and N. Cherbuin (2009). "Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies." Am J Geriatr Psychiatry 17(7): 542-555.
Association, A. s. (2016). "2016 Alzheimer''s disease facts and figures." Alzheimer''s & Dementia 12(4): 459-509.
Ayers-Ringler, J. R., Y. F. Jia, Y. Y. Qiu and D. S. Choi (2016). "Role of astrocytic glutamate transporter in alcohol use disorder." World J Psychiatry 6(1): 31-42.
Ballabh, P., A. Braun and M. Nedergaard (2004). "The blood-brain barrier: an overview: structure, regulation, and clinical implications." Neurobiol Dis 16(1): 1-13.
Basciano, H., L. Federico and K. Adeli (2005). "Fructose, insulin resistance, and metabolic dyslipidemia." Nutrition & metabolism 2(1): 1.
Bekinschtein, P., M. Cammarota, C. Katche, L. Slipczuk, J. I. Rossato, A. Goldin, I. Izquierdo and J. H. Medina (2008). "BDNF is essential to promote persistence of long-term memory storage." Proc Natl Acad Sci U S A 105(7): 2711-2716.
Best, C. H., W. S. Hartroft and et al. (1949). "Liver damage produced by feeding alcohol or sugar and its prevention by choline." Br Med J 2(4635): 1002-1006, pl.
Blyth, B. J., A. Farhavar, C. Gee, B. Hawthorn, H. He, A. Nayak, V. Stocklein and J. J. Bazarian (2009). "Validation of serum markers for blood-brain barrier disruption in traumatic brain injury." J Neurotrauma 26(9): 1497-1507.
Bonda, D. J., X. Wang, G. Perry, A. Nunomura, M. Tabaton, X. Zhu and M. A. Smith (2010). "Oxidative stress in Alzheimer disease: a possibility for prevention." Neuropharmacology 59(4-5): 290-294.
Bowling, A. C., E. M. Mutisya, L. C. Walker, D. L. Price, L. C. Cork and M. F. Beal (1993). "Age-dependent impairment of mitochondrial function in primate brain." J Neurochem 60(5): 1964-1967.
Bracken, M. B. (2007). "Rosiglitazone and cardiovascular risk." N Engl J Med 357(9): 937-938; author reply 939-940.
Brett, A. S. (2007). "Rosiglitazone and cardiovascular risk." N Engl J Med 357(9): 939; author reply 939-940.
Caceres, M., J. Lachuer, M. A. Zapala, J. C. Redmond, L. Kudo, D. H. Geschwind, D. J. Lockhart, T. M. Preuss and C. Barlow (2003). "Elevated gene expression levels distinguish human from non-human primate brains." Proc Natl Acad Sci U S A 100(22): 13030-13035.
Cai, H., W. N. Cong, S. Ji, S. Rothman, S. Maudsley and B. Martin (2012). "Metabolic dysfunction in Alzheimer''s disease and related neurodegenerative disorders." Curr Alzheimer Res 9(1): 5-17.
Camandola, S. and M. P. Mattson (2017). "Brain metabolism in health, aging, and neurodegeneration." EMBO J 36(11): 1474-1492.
Cargiulo, T. (2007). "Understanding the health impact of alcohol dependence." Am J Health Syst Pharm 64(5 Suppl 3): S5-11.
Chastain, L. G. and D. K. Sarkar (2014). "Role of microglia in regulation of ethanol neurotoxic action." Int Rev Neurobiol 118: 81-103.
Chen, C. H., C. H. Pan, C. C. Chen and M. C. Huang (2011). "Increased oxidative DNA damage in patients with alcohol dependence and its correlation with alcohol withdrawal severity." Alcohol Clin Exp Res 35(2): 338-344.
Chou, L. M., C. I. Lin, Y. H. Chen, H. Liao and S. H. Lin (2016). "A diet containing grape powder ameliorates the cognitive decline in aged rats with a long-term high-fructose-high-fat dietary pattern." J Nutr Biochem 34: 52-60.
Correia, S. C., R. X. Santos, C. Carvalho, S. Cardoso, E. Candeias, M. S. Santos, C. R. Oliveira and P. I. Moreira (2012). "Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer''s disease and diabetes interrelation." Brain Res 1441: 64-78.
Crews, F., K. Nixon, D. Kim, J. Joseph, B. Shukitt-Hale, L. Qin and J. Zou (2006). "BHT blocks NF-kappaB activation and ethanol-induced brain damage." Alcohol Clin Exp Res 30(11): 1938-1949.
Crews, F. T., C. J. Braun, B. Hoplight, R. C. Switzer, 3rd and D. J. Knapp (2000). "Binge ethanol consumption causes differential brain damage in young adolescent rats compared with adult rats." Alcohol Clin Exp Res 24(11): 1712-1723.
Crews, F. T. and K. Nixon (2009). "Mechanisms of neurodegeneration and regeneration in alcoholism." Alcohol Alcohol 44(2): 115-127.
Crews, F. T. and R. P. Vetreno (2011). "Addiction, adolescence, and innate immune gene induction." Front Psychiatry 2: 19.
Crews, F. T., J. Zou and L. Qin (2011). "Induction of innate immune genes in brain create the neurobiology of addiction." Brain Behav Immun 25 Suppl 1: S4-S12.
Dalsgaard, M. K., B. Quistorff, E. R. Danielsen, C. Selmer, T. Vogelsang and N. H. Secher (2004). "A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain." J Physiol 554(Pt 2): 571-578.
de Chaves, E. P. and V. Narayanaswami (2008). "Apolipoprotein E and cholesterol in aging and disease in the brain." Future Lipidol 3(5): 505-530.
de la, M. H. P., C. S. Lieber, L. M. DeCarli, S. W. French, K. O. Lindros, H. Jarvelainen, C. Bode, A. Parlesak and J. C. Bode (2001). "Models of alcoholic liver disease in rodents: a critical evaluation." Alcohol Clin Exp Res 25(5 Suppl ISBRA): 254S-261S.
de la Monte, S. M. (2012). "Brain insulin resistance and deficiency as therapeutic targets in Alzheimer''s disease." Curr Alzheimer Res 9(1): 35-66.
De La Monte, S. M. (2012). "Metabolic derangements mediate cognitive impairment and Alzheimer''s disease: role of peripheral insulin-resistance diseases." Panminerva Med 54(3): 171-178.
de la Monte, S. M., M. Tong, N. Lester-Coll, M. Plater, Jr. and J. R. Wands (2006). "Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer''s disease." J Alzheimers Dis 10(1): 89-109.
de Leon, M. J., S. H. Ferris, A. E. George, B. Reisberg, D. R. Christman, Kricheff, II and A. P. Wolf (1983). "Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer''s disease." J Cereb Blood Flow Metab 3(3): 391-394.
Del Rio, D., A. Rodriguez-Mateos, J. P. Spencer, M. Tognolini, G. Borges and A. Crozier (2013). "Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases." Antioxid Redox Signal 18(14): 1818-1892.
Ding, F., J. Yao, J. R. Rettberg, S. Chen and R. D. Brinton (2013). "Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer''s mouse brain: implication for bioenergetic intervention." PLoS One 8(11): e79977.
Dixon, J. B. (2010). "The effect of obesity on health outcomes." Mol Cell Endocrinol 316(2): 104-108.
Eggler, A. L., K. A. Gay and A. D. Mesecar (2008). "Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2." Mol Nutr Food Res 52 Suppl 1: S84-94.
Ehrlich, D. and C. Humpel (2012). "Chronic vascular risk factors (cholesterol, homocysteine, ethanol) impair spatial memory, decline cholinergic neurons and induce blood-brain barrier leakage in rats in vivo." J Neurol Sci 322(1-2): 92-95.
Ehrlich, D., M. Pirchl and C. Humpel (2012). "Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats." Neuroscience 205: 154-166.
European Standards Committee on Oxidative, D. N. A. D. (2003). "Measurement of DNA oxidation in human cells by chromatographic and enzymic methods." Free Radic Biol Med 34(8): 1089-1099.
Fabiani, M., K. A. Low, C. H. Tan, B. Zimmerman, M. A. Fletcher, N. Schneider-Garces, E. L. Maclin, A. M. Chiarelli, B. P. Sutton and G. Gratton (2014). "Taking the pulse of aging: mapping pulse pressure and elasticity in cerebral arteries with optical methods." Psychophysiology 51(11): 1072-1088.
Farr, S. A., K. A. Yamada, D. A. Butterfield, H. M. Abdul, L. Xu, N. E. Miller, W. A. Banks and J. E. Morley (2008). "Obesity and hypertriglyceridemia produce cognitive impairment." Endocrinology 149(5): 2628-2636.
Fernandez, G. M., W. N. Stewart and L. M. Savage (2016). "Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure." PLoS One 11(3): e0149987.
Fernandez, I., A. Pena, N. Del Teso, V. Perez and J. Rodriguez-Cuesta (2010). "Clinical biochemistry parameters in C57BL/6J mice after blood collection from the submandibular vein and retroorbital plexus." J Am Assoc Lab Anim Sci 49(2): 202-206.
Ferruzzi, M. G., J. K. Lobo, E. M. Janle, B. Cooper, J. E. Simon, Q. L. Wu, C. Welch, L. Ho, C. Weaver and G. M. Pasinetti (2009). "Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer''s disease." J Alzheimers Dis 18(1): 113-124.
Fraga, C. G. and P. I. Oteiza (2011). "Dietary flavonoids: Role of (-)-epicatechin and related procyanidins in cell signaling." Free Radic Biol Med 51(4): 813-823.
Franke, H. (1995). "Influence of chronic alcohol treatment on the GFAP-immunoreactivity in astrocytes of the hippocampus in rats." Acta Histochem 97(3): 263-271.
Freude, S., L. Plum, J. Schnitker, U. Leeser, M. Udelhoven, W. Krone, J. C. Bruning and M. Schubert (2005). "Peripheral hyperinsulinemia promotes tau phosphorylation in vivo." Diabetes 54(12): 3343-3348.
Fujimura, M., Y. Gasche, Y. Morita-Fujimura, J. Massengale, M. Kawase and P. H. Chan (1999). "Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion." Brain Res 842(1): 92-100.
Gage, F. H., P. A. Kelly and A. Bjorklund (1984). "Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats." J Neurosci 4(11): 2856-2865.
Gaitonde, M. K., E. Evison and G. M. Evans (1983). "The rate of utilization of glucose via hexosemonophosphate shunt in brain." J Neurochem 41(5): 1253-1260.
Gasser, A. and J. M. Forbes (2008). "Advanced glycation: implications in tissue damage and disease." Protein Pept Lett 15(4): 385-391.
Gatta, E., T. Lefebvre, S. Gaetani, M. Dos Santos, J. Marrocco, A.-M. Mir, T. Cassano, S. Maccari, F. Nicoletti and J. Mairesse (2016). "Evidence for an imbalance between tau O-GlcNAcylation and phosphorylation in the hippocampus of a mouse model of Alzheimer’s disease." Pharmacological research 105: 186-197.
Georgiev, V., A. Ananga and V. Tsolova (2014). "Recent advances and uses of grape flavonoids as nutraceuticals." Nutrients 6(1): 391-415.
Ghadernezhad, N., L. Khalaj, H. Pazoki-Toroudi, M. Mirmasoumi and G. Ashabi (2016). "Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway." Pharmaceutical biology: 1-9.
Giordano, G., M. Guizzetti, K. Dao, H. A. Mattison and L. G. Costa (2011). "Ethanol impairs muscarinic receptor-induced neuritogenesis in rat hippocampal slices: Role of astrocytes and extracellular matrix proteins." Biochem Pharmacol 82(11): 1792-1799.
Glisky, E. L. (2007). Changes in Cognitive Function in Human Aging. Brain Aging: Models, Methods, and Mechanisms. D. R. Riddle. Boca Raton (FL).
Grossman, L. I., T. R. Schmidt, D. E. Wildman and M. Goodman (2001). "Molecular evolution of aerobic energy metabolism in primates." Mol Phylogenet Evol 18(1): 26-36.
Grossman, L. I., D. E. Wildman, T. R. Schmidt and M. Goodman (2004). "Accelerated evolution of the electron transport chain in anthropoid primates." Trends Genet 20(11): 578-585.
Grosso, G., U. Stepaniak, A. Micek, M. Kozela, D. Stefler, M. Bobak and A. Pajak (2017). "Dietary polyphenol intake and risk of type 2 diabetes in the Polish arm of the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study." Br J Nutr 118(1): 60-68.
Guindon, K. A., L. L. Bedard and T. E. Massey (2007). "Elevation of 8-hydroxydeoxyguanosine in DNA from isolated mouse lung cells following in vivo treatment with aflatoxin B(1)." Toxicol Sci 98(1): 57-62.
Guttmann, C. R., F. A. Jolesz, R. Kikinis, R. J. Killiany, M. B. Moss, T. Sandor and M. S. Albert (1998). "White matter changes with normal aging." Neurology 50(4): 972-978.
Haapasalo, A., I. Sipola, K. Larsson, K. E. Åkerman, P. Stoilov, S. Stamm, G. Wong and E. Castrén (2002). "Regulation of TRKB surface expression by brain-derived neurotrophic factor and truncated TRKB isoforms." Journal of Biological Chemistry 277(45): 43160-43167.
Habgood, M. D., N. Bye, K. M. Dziegielewska, C. J. Ek, M. A. Lane, A. Potter, C. Morganti-Kossmann and N. R. Saunders (2007). "Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice." Eur J Neurosci 25(1): 231-238.
Hagberg, H., C. Mallard, D. M. Ferriero, S. J. Vannucci, S. W. Levison, Z. S. Vexler and P. Gressens (2015). "The role of inflammation in perinatal brain injury." Nat Rev Neurol 11(4): 192-208.
Hall, P. M. (1992). "Genetic and acquired factors that influence individual susceptibility to alcohol-associated liver disease." J Gastroenterol Hepatol 7(4): 417-426.
Harris, J. J., R. Jolivet and D. Attwell (2012). "Synaptic energy use and supply." Neuron 75(5): 762-777.
Hassing, L. B., A. K. Dahl, V. Thorvaldsson, S. Berg, M. Gatz, N. L. Pedersen and B. Johansson (2009). "Overweight in midlife and risk of dementia: a 40-year follow-up study." Int J Obes (Lond) 33(8): 893-898.
Haygood, R., O. Fedrigo, B. Hanson, K. D. Yokoyama and G. A. Wray (2007). "Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution." Nat Genet 39(9): 1140-1144.
Hedden, T. and J. D. Gabrieli (2004). "Insights into the ageing mind: a view from cognitive neuroscience." Nat Rev Neurosci 5(2): 87-96.
Hoyer, S. (1982). "The abnormally aged brain. Its blood flow and oxidative metabolism. A review - part II." Arch Gerontol Geriatr 1(3): 195-207.
Hoyer, S. (1982). "Normal and abnormal circulation and oxidative metabolism in the aging human brain." J Cereb Blood Flow Metab 2 Suppl 1: S10-13.
Hoyer, S. (1982). "The young-adult and normally aged brain. Its blood flow and oxidative metabolism. A review--part I." Arch Gerontol Geriatr 1(2): 101-116.
Huang, E. J. and L. F. Reichardt (2001). "Neurotrophins: roles in neuronal development and function." Annu Rev Neurosci 24: 677-736.
Huang, Y. Z. and J. O. McNamara (2012). "Neuroprotective effects of reactive oxygen species mediated by BDNF-independent activation of TrkB." The Journal of Neuroscience 32(44): 15521-15532.
Iseri, O. A., C. S. Lieber and L. S. Gottlieb (1966). "The ultrastructure of fatty liver induced by prolonged ethanol ingestion." Am J Pathol 48(4): 535-555.
Kalev-Zylinska, M. L. and M. J. During (2007). "Paradoxical facilitatory effect of low-dose alcohol consumption on memory mediated by NMDA receptors." J Neurosci 27(39): 10456-10467.
Kamat, P. K., C. J. Mallonee, A. K. George, S. C. Tyagi and N. Tyagi (2016). "Homocysteine, Alcoholism, and Its Potential Epigenetic Mechanism." Alcohol Clin Exp Res 40(12): 2474-2481.
Kaspar, J. W., S. K. Niture and A. K. Jaiswal (2009). "Nrf2: INrf2 (Keap1) signaling in oxidative stress." Free Radical Biology and Medicine 47(9): 1304-1309.
Kaspar, J. W., S. K. Niture and A. K. Jaiswal (2012). "Antioxidant-induced INrf2 (Keap1) tyrosine 85 phosphorylation controls the nuclear export and degradation of the INrf2–Cul3–Rbx1 complex to allow normal Nrf2 activation and repression." J Cell Sci 125(4): 1027-1038.
Kim, B. and E. L. Feldman (2015). "Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome." Experimental & molecular medicine 47(3): e149.
Kim, H. S., M. J. Quon and J. A. Kim (2014). "New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate." Redox Biol 2: 187-195.
Kivipelto, M., T. Ngandu, L. Fratiglioni, M. Viitanen, I. Kareholt, B. Winblad, E. L. Helkala, J. Tuomilehto, H. Soininen and A. Nissinen (2005). "Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease." Arch Neurol 62(10): 1556-1560.
Kivipelto, M., T. Ngandu, T. Laatikainen, B. Winblad, H. Soininen and J. Tuomilehto (2006). "Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study." Lancet Neurol 5(9): 735-741.
Kivipelto, M. and A. Solomon (2006). "Cholesterol as a risk factor for Alzheimer''s disease - epidemiological evidence." Acta Neurol Scand Suppl 185: 50-57.
Klegeris, A. and P. L. McGeer (1997). "beta-amyloid protein enhances macrophage production of oxygen free radicals and glutamate." J Neurosci Res 49(2): 229-235.
Klegeris, A., D. G. Walker and P. L. McGeer (1997). "Interaction of Alzheimer beta-amyloid peptide with the human monocytic cell line THP-1 results in a protein kinase C-dependent secretion of tumor necrosis factor-alpha." Brain Res 747(1): 114-121.
Kobayashi, M. and M. Yamamoto (2006). "Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species." Adv Enzyme Regul 46: 113-140.
Kojro, E., R. Postina, C. Buro, C. Meiringer, K. Gehrig-Burger and F. Fahrenholz (2006). "The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein." FASEB J 20(3): 512-514.
Koob, G. F. and N. D. Volkow (2010). "Neurocircuitry of addiction." Neuropsychopharmacology 35(1): 217-238.
Krikorian, R., T. A. Nash, M. D. Shidler, B. Shukitt-Hale and J. A. Joseph (2010). "Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment." Br J Nutr 103(5): 730-734.
Kuhl, D. E., E. J. Metter, W. H. Riege and R. A. Hawkins (1984). "The effect of normal aging on patterns of local cerebral glucose utilization." Ann Neurol 15 Suppl: S133-137.
Kumar, R., P. Chaterjee, P. K. Sharma, A. K. Singh, A. Gupta, K. Gill, M. Tripathi, A. B. Dey and S. Dey (2013). "Sirtuin1: a promising serum protein marker for early detection of Alzheimer''s disease." PLoS One 8(4): e61560.
Lasek, A. W. (2016). "Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder." Alcohol Clin Exp Res 40(10): 2030-2042.
Lester-Coll, N., E. J. Rivera, S. J. Soscia, K. Doiron, J. R. Wands and S. M. de la Monte (2006). "Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer''s disease." J Alzheimers Dis 9(1): 13-33.
Leu, J. G., C. Y. Lin, J. H. Jian, C. Y. Shih and Y. J. Liang (2013). "Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells." An Acad Bras Cienc 85(2): 745-752.
Li, C. S., K. Y. Wu, G. P. Chang-Chien and C. C. Chou (2005). "Analysis of oxidative DNA damage 8-hydroxy-2''-deoxyguanosine as a biomarker of exposures to persistent pollutants for marine mammals." Environ Sci Technol 39(8): 2455-2460.
Li, H., T. Qin, M. Li and S. Ma (2016). "Thymol improves high-fat diet-induced cognitive deficits in mice via ameliorating brain insulin resistance and upregulating NRF2/HO-1 pathway." Metabolic Brain Disease: 1-9.
Li, J. and A. M. Schmidt (1997). "Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products." J Biol Chem 272(26): 16498-16506.
Liao, C. W., W. L. Cho, T. C. Kao, K. E. Su, Y. H. Lin and C. K. Fan (2008). "Blood-brain barrier impairment with enhanced SP, NK-1R, GFAP and claudin-5 expressions in experimental cerebral toxocariasis." Parasite Immunol 30(10): 525-534.
Lieber, C. S., J. M. Lasker, L. M. DeCarli, J. Saeli and T. Wojtowicz (1988). "Role of acetone, dietary fat and total energy intake in induction of hepatic microsomal ethanol oxidizing system." J Pharmacol Exp Ther 247(2): 791-795.
Liu, F., K. Iqbal, I. Grundke-Iqbal, G. W. Hart and C. X. Gong (2004). "O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer''s disease." Proc Natl Acad Sci U S A 101(29): 10804-10809.
Liu, F., J. Shi, H. Tanimukai, J. Gu, J. Gu, I. Grundke-Iqbal, K. Iqbal and C.-X. Gong (2009). "Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer''s disease." Brain: awp099.
Liu, F., J. Shi, H. Tanimukai, J. Gu, J. Gu, I. Grundke-Iqbal, K. Iqbal and C. X. Gong (2009). "Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer''s disease." Brain 132(Pt 7): 1820-1832.
Liu, L. and X. D. Liu (2014). "Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances." Front Pharmacol 5: 273.
Liu, Q., F. Xie, S. Siedlak, A. Nunomura, K. Honda, P. Moreira, X. Zhua, M. Smith and G. Perry (2004). "Neurofilament proteins in neurodegenerative diseases." Cellular and Molecular Life Sciences CMLS 61(24): 3057-3075.
Liu, Y., F. Liu, I. Grundke-Iqbal, K. Iqbal and C. X. Gong (2009). "Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer''s disease." J Neurochem 111(1): 242-249.
Logrip, M. L., S. Barak, V. Warnault and D. Ron (2015). "Corticostriatal BDNF and alcohol addiction." Brain Res 1628(Pt A): 60-67.
Lozano, I., R. Van der Werf, W. Bietiger, E. Seyfritz, C. Peronet, M. Pinget, N. Jeandidier, E. Maillard, E. Marchioni and S. Sigrist (2016). "High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications." Nutrition & metabolism 13(1): 1.
Lu, J., Y. L. Zheng, D. M. Wu, D. X. Sun, Q. Shan and S. H. Fan (2006). "Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis." FEBS Lett 580(28-29): 6730-6740.
Lu, Y. C., W. C. Yeh and P. S. Ohashi (2008). "LPS/TLR4 signal transduction pathway." Cytokine 42(2): 145-151.
Lue, L. F., D. G. Walker, L. Brachova, T. G. Beach, J. Rogers, A. M. Schmidt, D. M. Stern and S. D. Yan (2001). "Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer''s disease: identification of a cellular activation mechanism." Exp Neurol 171(1): 29-45.
Luevano-Contreras, C. and K. Chapman-Novakofski (2010). "Dietary advanced glycation end products and aging." Nutrients 2(12): 1247-1265.
Lyn-Cook, L. E., Jr., M. Lawton, M. Tong, E. Silbermann, L. Longato, P. Jiao, P. Mark, J. R. Wands, H. Xu and S. M. de la Monte (2009). "Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in type 2 diabetes and non-alcoholic steatohepatitis." J Alzheimers Dis 16(4): 715-729.
Ma, Q. (2013). "Role of nrf2 in oxidative stress and toxicity." Annu Rev Pharmacol Toxicol 53: 401-426.
MacLennan, A. J., N. Lee and D. W. Walker (1995). "Chronic ethanol administration decreases brain-derived neurotrophic factor gene expression in the rat hippocampus." Neurosci Lett 197(2): 105-108.
Maghsoudi, Z., R. Ghiasvand and A. Salehi-Abargouei (2016). "Empirically derived dietary patterns and incident type 2 diabetes mellitus: a systematic review and meta-analysis on prospective observational studies." Public Health Nutr 19(2): 230-241.
Mangialasche, F., A. Solomon, B. Winblad, P. Mecocci and M. Kivipelto (2010). "Alzheimer''s disease: clinical trials and drug development." Lancet Neurol 9(7): 702-716.
Marchi, N., P. Rasmussen, M. Kapural, V. Fazio, K. Kight, M. R. Mayberg, A. Kanner, B. Ayumar, B. Albensi, M. Cavaglia and D. Janigro (2003). "Peripheral markers of brain damage and blood-brain barrier dysfunction." Restor Neurol Neurosci 21(3-4): 109-121.
Marra, F., A. Gastaldelli, G. Svegliati Baroni, G. Tell and C. Tiribelli (2008). "Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis." Trends Mol Med 14(2): 72-81.
Marshall, S. A., J. A. McClain, M. L. Kelso, D. M. Hopkins, J. R. Pauly and K. Nixon (2013). "Microglial activation is not equivalent to neuroinflammation in alcohol-induced neurodegeneration: The importance of microglia phenotype." Neurobiol Dis 54: 239-251.
Mash, D. C., J. ffrench-Mullen, N. Adi, Y. Qin, A. Buck and J. Pablo (2007). "Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling." PLoS One 2(11): e1187.
Matsuzawa-Nagata, N., T. Takamura, H. Ando, S. Nakamura, S. Kurita, H. Misu, T. Ota, M. Yokoyama, M. Honda, K. Miyamoto and S. Kaneko (2008). "Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity." Metabolism 57(8): 1071-1077.
Mattay, V. S., F. Fera, A. Tessitore, A. R. Hariri, K. F. Berman, S. Das, A. Meyer-Lindenberg, T. E. Goldberg, J. H. Callicott and D. R. Weinberger (2006). "Neurophysiological correlates of age-related changes in working memory capacity." Neurosci Lett 392(1-2): 32-37.
Mattson, M. P., W. A. Pedersen, W. Duan, C. Culmsee and S. Camandola (1999). "Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer''s and Parkinson''s diseases." Ann N Y Acad Sci 893: 154-175.
Montagne, A., S. R. Barnes, M. D. Sweeney, M. R. Halliday, A. P. Sagare, Z. Zhao, A. W. Toga, R. E. Jacobs, C. Y. Liu, L. Amezcua, M. G. Harrington, H. C. Chui, M. Law and B. V. Zlokovic (2015). "Blood-brain barrier breakdown in the aging human hippocampus." Neuron 85(2): 296-302.
Montesinos, J., S. Alfonso-Loeches and C. Guerri (2016). "Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System." Alcohol Clin Exp Res 40(11): 2260-2270.
Moosavi, F., R. Hosseini, L. Saso and O. Firuzi (2016). "Modulation of neurotrophic signaling pathways by polyphenols." Drug design, development and therapy 10: 23.
Morris, R. (1984). "Developments of a water-maze procedure for studying spatial learning in the rat." J Neurosci Methods 11(1): 47-60.
Mostofsky, E., M. R. Burger, G. Schlaug, K. J. Mukamal, W. D. Rosamond and M. A. Mittleman (2010). "Alcohol and acute ischemic stroke onset: the stroke onset study." Stroke 41(9): 1845-1849.
Mullen, W., S. C. Marks and A. Crozier (2007). "Evaluation of phenolic compounds in commercial fruit juices and fruit drinks." J Agric Food Chem 55(8): 3148-3157.
Nagahama, Y., H. Nabatame, T. Okina, H. Yamauchi, M. Narita, N. Fujimoto, M. Murakami, H. Fukuyama and M. Matsuda (2003). "Cerebral correlates of the progression rate of the cognitive decline in probable Alzheimer''s disease." Eur Neurol 50(1): 1-9.
Nagai, Y., S. Yonemitsu, D. M. Erion, T. Iwasaki, R. Stark, D. Weismann, J. Dong, D. Zhang, M. J. Jurczak, M. G. Loffler, J. Cresswell, X. X. Yu, S. F. Murray, S. Bhanot, B. P. Monia, J. S. Bogan, V. Samuel and G. I. Shulman (2009). "The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance." Cell Metab 9(3): 252-264.
Nagy, V., O. Bozdagi, A. Matynia, M. Balcerzyk, P. Okulski, J. Dzwonek, R. M. Costa, A. J. Silva, L. Kaczmarek and G. W. Huntley (2006). "Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory." J Neurosci 26(7): 1923-1934.
Nehlig, A. and A. Pereira de Vasconcelos (1993). "Glucose and ketone body utilization by the brain of neonatal rats." Prog Neurobiol 40(2): 163-221.
Niccoli, T., M. Cabecinha, A. Tillmann, F. Kerr, C. T. Wong, D. Cardenes, A. J. Vincent, L. Bettedi, L. Li and S. Grönke (2016). "Increased glucose transport into neurons rescues Aβ toxicity in Drosophila." Current Biology 26(17): 2291-2300.
Nissen, S. E. and K. Wolski (2007). "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes." N Engl J Med 356(24): 2457-2471.
Niture, S. K., R. Khatri and A. K. Jaiswal (2014). "Regulation of Nrf2—an update." Free Radical Biology and Medicine 66: 36-44.
Okonkwo, D. O., J. K. Yue, A. M. Puccio, D. M. Panczykowski, T. Inoue, P. J. McMahon, M. D. Sorani, E. L. Yuh, H. F. Lingsma, A. I. Maas, A. B. Valadka, G. T. Manley, R. Transforming and I. Clinical Knowledge in Traumatic Brain Injury (2013). "GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study." J Neurotrauma 30(17): 1490-1497.
Okulski, P., T. M. Jay, J. Jaworski, K. Duniec, J. Dzwonek, F. A. Konopacki, G. M. Wilczynski, A. Sanchez-Capelo, J. Mallet and L. Kaczmarek (2007). "TIMP-1 abolishes MMP-9-dependent long-lasting long-term potentiation in the prefrontal cortex." Biol Psychiatry 62(4): 359-362.
Oudega, M. (2012). "Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair." Cell Tissue Res 349(1): 269-288.
Panchal, S. K., H. Poudyal, A. Iyer, R. Nazer, M. A. Alam, V. Diwan, K. Kauter, C. Sernia, F. Campbell, L. Ward, G. Gobe, A. Fenning and L. Brown (2011). "High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats." J Cardiovasc Pharmacol 57(5): 611-624.
Pandey, S. C. (2016). "A Critical Role of Brain-Derived Neurotrophic Factor in Alcohol Consumption." Biol Psychiatry 79(6): 427-429.
Pascual, M., P. Balino, C. M. Aragon and C. Guerri (2015). "Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: role of TLR4 and TLR2." Neuropharmacology 89: 352-359.
Pasquier, F., A. Boulogne, D. Leys and P. Fontaine (2006). "Diabetes mellitus and dementia." Diabetes Metab 32(5 Pt 1): 403-414.
Patapoutian, A. and L. F. Reichardt (2001). "Trk receptors: mediators of neurotrophin action." Curr Opin Neurobiol 11(3): 272-280.
Patil, S., P. Jain, P. Ghumatkar, R. Tambe and S. Sathaye (2014). "Neuroprotective effect of metformin in MPTP-induced Parkinson’s disease in mice." Neuroscience 277: 747-754.
Pezzuto, J. M. (2008). "Grapes and human health: a perspective." J Agric Food Chem 56(16): 6777-6784.
Pontzer, H., M. H. Brown, D. A. Raichlen, H. Dunsworth, B. Hare, K. Walker, A. Luke, L. R. Dugas, R. Durazo-Arvizu, D. Schoeller, J. Plange-Rhule, P. Bovet, T. E. Forrester, E. V. Lambert, M. E. Thompson, R. W. Shumaker and S. R. Ross (2016). "Metabolic acceleration and the evolution of human brain size and life history." Nature 533(7603): 390-392.
Powers, J. M., W. W. Schlaepfer, M. C. Willingham and B. J. Hall (1981). "An immunoperoxidase study of senile cerebral amyloidosis with pathogenetic considerations." J Neuropathol Exp Neurol 40(6): 592-612.
Prasad, S., R. K. Sajja, P. Naik and L. Cucullo (2014). "Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview." J Pharmacovigil 2(2): 125.
Procaccini, C., M. Santopaolo, D. Faicchia, A. Colamatteo, L. Formisano, P. de Candia, M. Galgani, V. De Rosa and G. Matarese (2016). "Role of metabolism in neurodegenerative disorders." Metabolism 65(9): 1376-1390.
Provias, J. and B. Jeynes (2014). "The role of the blood-brain barrier in the pathogenesis of senile plaques in Alzheimer''s disease." Int J Alzheimers Dis 2014: 191863.
Rakic, P. (2009). "Evolution of the neocortex: a perspective from developmental biology." Nat Rev Neurosci 10(10): 724-735.
Ramsey, R. B., J. P. Jones, S. H. Naqvi and H. J. Nicholas (1971). "The biosynthesis of cholesterol and other sterols by brain tissue. I. Subcellular biosynthesis in vitro." Lipids 6(3): 154-161.
Rector, R. S., J. P. Thyfault, Y. Wei and J. A. Ibdah (2008). "Non-alcoholic fatty liver disease and the metabolic syndrome: an update." World J Gastroenterol 14(2): 185-192.
Resnick, S. M., D. L. Pham, M. A. Kraut, A. B. Zonderman and C. Davatzikos (2003). "Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain." J Neurosci 23(8): 3295-3301.
Rosenberg, G. A. (2012). "Neurological diseases in relation to the blood-brain barrier." J Cereb Blood Flow Metab 32(7): 1139-1151.
Rosenzweig, E. S. and C. A. Barnes (2003). "Impact of aging on hippocampal function: plasticity, network dynamics, and cognition." Prog Neurobiol 69(3): 143-179.
Rubio-Araiz, A., F. Porcu, M. Perez-Hernandez, M. S. Garcia-Gutierrez, M. A. Aracil-Fernandez, M. D. Gutierrez-Lopez, C. Guerri, J. Manzanares, E. O''Shea and M. I. Colado (2016). "Disruption of blood-brain barrier integrity in postmortem alcoholic brain: preclinical evidence of TLR4 involvement from a binge-like drinking model." Addict Biol.
Samochowiec, A., A. Grzywacz, L. Kaczmarek, P. Bienkowski, J. Samochowiec, P. Mierzejewski, U. W. Preuss, E. Grochans and A. Ciechanowicz (2010). "Functional polymorphism of matrix metalloproteinase-9 (MMP-9) gene in alcohol dependence: family and case control study." Brain Res 1327: 103-106.
Sasaki, K., S. Chiba and F. Yoshizaki (2014). "Effect of natural flavonoids, stilbenes and caffeic acid oligomers on protein glycation." Biomed Rep 2(5): 628-632.
Schoknecht, K., Y. David and U. Heinemann (2015). "The blood-brain barrier-gatekeeper to neuronal homeostasis: clinical implications in the setting of stroke." Semin Cell Dev Biol 38: 35-42.
Sengupta, P. (2013). "The Laboratory Rat: Relating Its Age With Human''s." Int J Prev Med 4(6): 624-630.
Shukitt-Hale, B., A. Carey, L. Simon, D. A. Mark and J. A. Joseph (2006). "Effects of Concord grape juice on cognitive and motor deficits in aging." Nutrition 22(3): 295-302.
Shukitt-Hale, B., F. C. Lau and J. A. Joseph (2008). "Berry fruit supplementation and the aging brain." J Agric Food Chem 56(3): 636-641.
Singh, A. K., Y. Jiang, S. Gupta and E. Benlhabib (2007). "Effects of chronic ethanol drinking on the blood brain barrier and ensuing neuronal toxicity in alcohol-preferring rats subjected to intraperitoneal LPS injection." Alcohol Alcohol 42(5): 385-399.
Small, G. W., L. M. Ercoli, D. H. Silverman, S. C. Huang, S. Komo, S. Y. Bookheimer, H. Lavretsky, K. Miller, P. Siddarth, N. L. Rasgon, J. C. Mazziotta, S. Saxena, H. M. Wu, M. S. Mega, J. L. Cummings, A. M. Saunders, M. A. Pericak-Vance, A. D. Roses, J. R. Barrio and M. E. Phelps (2000). "Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer''s disease." Proc Natl Acad Sci U S A 97(11): 6037-6042.
Sommerfeld, M. T., R. Schweigreiter, Y.-A. Barde and E. Hoppe (2000). "Down-regulation of the Neurotrophin Receptor TrkB following Ligand Binding EVIDENCE FOR AN INVOLVEMENT OF THE PROTEASOME AND DIFFERENTIAL REGULATION OF TrkA AND TrkB." Journal of Biological Chemistry 275(12): 8982-8990.
Sowell, E. R., B. S. Peterson, P. M. Thompson, S. E. Welcome, A. L. Henkenius and A. W. Toga (2003). "Mapping cortical change across the human life span." Nat Neurosci 6(3): 309-315.
Spencer, J. P. (2009). "The impact of flavonoids on memory: physiological and molecular considerations." Chem Soc Rev 38(4): 1152-1161.
Spencer, J. P., D. Vauzour and C. Rendeiro (2009). "Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects." Arch Biochem Biophys 492(1-2): 1-9.
Spuch, C., S. Ortolano and C. Navarro (2012). "New insights in the amyloid-Beta interaction with mitochondria." J Aging Res 2012: 324968.
Sreeja, S., R. Geetha, E. Priyadarshini, K. Bhavani and C. V. Anuradha (2014). "Substitution of soy protein for casein prevents oxidative modification and inflammatory response induced in rats fed high fructose diet." ISRN Inflamm 2014: 641096.
Stahon, K. E., C. Bastian, S. Griffith, G. J. Kidd, S. Brunet and S. Baltan (2016). "Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter." J Neurosci 36(39): 9990-10001.
Steen, E., B. M. Terry, E. J. Rivera, J. L. Cannon, T. R. Neely, R. Tavares, X. J. Xu, J. R. Wands and S. M. de la Monte (2005). "Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer''s disease--is this type 3 diabetes?" J Alzheimers Dis 7(1): 63-80.
Stolp, H. B., C. J. Ek, P. A. Johansson, K. M. Dziegielewska, A. M. Potter, M. D. Habgood and N. R. Saunders (2007). "Effect of minocycline on inflammation-induced damage to the blood-brain barrier and white matter during development." Eur J Neurosci 26(12): 3465-3474.
Stranahan, A. M., E. D. Norman, K. Lee, R. G. Cutler, R. S. Telljohann, J. M. Egan and M. P. Mattson (2008). "Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats." Hippocampus 18(11): 1085-1088.
Studzinski, C. M., F. Li, A. J. Bruce-Keller, S. O. Fernandez-Kim, L. Zhang, A. M. Weidner, W. R. Markesbery, M. P. Murphy and J. N. Keller (2009). "Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice." J Neurochem 108(4): 860-866.
Subramaniam, S. and K. Unsicker (2010). "ERK and cell death: ERK1/2 in neuronal death." FEBS journal 277(1): 22-29.
Suwannaphet, W., A. Meeprom, S. Yibchok-Anun and S. Adisakwattana (2010). "Preventive effect of grape seed extract against high-fructose diet-induced insulin resistance and oxidative stress in rats." Food Chem Toxicol 48(7): 1853-1857.
Takeuchi, M. and S. Yamagishi (2009). "Involvement of toxic AGEs (TAGE) in the pathogenesis of diabetic vascular complications and Alzheimer''s disease." J Alzheimers Dis 16(4): 845-858.
Tanzi, R. E., R. D. Moir and S. L. Wagner (2004). "Clearance of Alzheimer''s Abeta peptide: the many roads to perdition." Neuron 43(5): 605-608.
Tapia-Arancibia, L., F. Rage, L. Givalois, P. Dingeon, S. Arancibia and F. Beauge (2001). "Effects of alcohol on brain-derived neurotrophic factor mRNA expression in discrete regions of the rat hippocampus and hypothalamus." J Neurosci Res 63(2): 200-208.
Thouennon, E., Y. Cheng, V. Falahatian, N. X. Cawley and Y. P. Loh (2015). "Rosiglitazone-activated PPARgamma induces neurotrophic factor-alpha1 transcription contributing to neuroprotection." J Neurochem 134(3): 463-470.
Turner, R. J. and F. R. Sharp (2016). "Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke." Front Cell Neurosci 10: 56.
Valavanidis, A., T. Vlachogianni and C. Fiotakis (2009). "8-hydroxy-2'' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis." J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27(2): 120-139.
Valles, S., J. Pitarch, J. Renau-Piqueras and C. Guerri (1997). "Ethanol exposure affects glial fibrillary acidic protein gene expression and transcription during rat brain development." J Neurochem 69(6): 2484-2493.
Valles, S. L., A. M. Blanco, M. Pascual and C. Guerri (2004). "Chronic ethanol treatment enhances inflammatory mediators and cell death in the brain and in astrocytes." Brain Pathol 14(4): 365-371.
van de Haar, H. J., S. Burgmans, P. A. Hofman, F. R. Verhey, J. F. Jansen and W. H. Backes (2015). "Blood-brain barrier impairment in dementia: current and future in vivo assessments." Neurosci Biobehav Rev 49: 71-81.
van de Haar, H. J., S. Burgmans, J. F. Jansen, M. J. van Osch, M. A. van Buchem, M. Muller, P. A. Hofman, F. R. Verhey and W. H. Backes (2016). "Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease." Radiology 281(2): 527-535.
Vargas, M. R. and J. A. Johnson (2009). "The Nrf2-ARE cytoprotective pathway in astrocytes." Expert Rev Mol Med 11: e17.
Verdelho, A., S. Madureira, J. M. Ferro, A. M. Basile, H. Chabriat, T. Erkinjuntti, F. Fazekas, M. Hennerici, J. O''Brien, L. Pantoni, E. Salvadori, P. Scheltens, M. C. Visser, L. O. Wahlund, G. Waldemar, A. Wallin, D. Inzitari and L. Study (2007). "Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study." J Neurol Neurosurg Psychiatry 78(12): 1325-1330.
Verzelloni, E., C. Pellacani, D. Tagliazucchi, S. Tagliaferri, L. Calani, L. G. Costa, F. Brighenti, G. Borges, A. Crozier, A. Conte and D. Del Rio (2011). "Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites." Mol Nutr Food Res 55 Suppl 1: S35-43.
Vrba, R., M. K. Gaitonde and D. Richter (1962). "The conversion of glucose carbon into protein in the brain and other organs of the rat." J Neurochem 9: 465-475.
Wang, S. W., Y. J. Wang, Y. J. Su, W. W. Zhou, S. G. Yang, R. Zhang, M. Zhao, Y. N. Li, Z. P. Zhang, D. W. Zhan and R. T. Liu (2012). "Rutin inhibits beta-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines." Neurotoxicology 33(3): 482-490.
Wang, X. P. and H. L. Ding (2008). "Alzheimer''s disease: epidemiology, genetics, and beyond." Neurosci Bull 24(2): 105-109.
Ward, M. A., C. M. Carlsson, M. A. Trivedi, M. A. Sager and S. C. Johnson (2005). "The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study." BMC Neurol 5: 23.
Waubant, E. (2006). "Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis." Dis Markers 22(4): 235-244.
Wilhelm, C. J. and M. Guizzetti (2015). "Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective." Front Integr Neurosci 9: 65.
Williams, R. J. and J. P. Spencer (2012). "Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease." Free Radic Biol Med 52(1): 35-45.
Williams, R. J., J. P. Spencer and C. Rice-Evans (2004). "Flavonoids: antioxidants or signalling molecules?" Free Radic Biol Med 36(7): 838-849.
Winkler, E. A., Y. Nishida, A. P. Sagare, S. V. Rege, R. D. Bell, D. Perlmutter, J. D. Sengillo, S. Hillman, P. Kong, A. R. Nelson, J. S. Sullivan, Z. Zhao, H. J. Meiselman, R. B. Wendy, J. Soto, E. D. Abel, J. Makshanoff, E. Zuniga, D. C. De Vivo and B. V. Zlokovic (2015). "GLUT1 reductions exacerbate Alzheimer''s disease vasculo-neuronal dysfunction and degeneration." Nat Neurosci 18(4): 521-530.
Wolf, P. A., A. Beiser, M. F. Elias, R. Au, R. S. Vasan and S. Seshadri (2007). "Relation of obesity to cognitive function: importance of central obesity and synergistic influence of concomitant hypertension. The Framingham Heart Study." Curr Alzheimer Res 4(2): 111-116.
Wong, R. H., C. Y. Yeh, Y. M. Hsueh, J. D. Wang, Y. C. Lei and T. J. Cheng (2003). "Association of hepatitis virus infection, alcohol consumption and plasma vitamin A levels with urinary 8-hydroxydeoxyguanosine in chemical workers." Mutat Res 535(2): 181-186.
Wu, C., S. T. Chen, K. H. Peng, T. J. Cheng and K. Y. Wu (2016). "Concurrent quantification of multiple biomarkers indicative of oxidative stress status using liquid chromatography-tandem mass spectrometry." Anal Biochem 512: 26-35.
Wu, K. Y., N. Scheller, A. Ranasinghe, T. Y. Yen, R. Sangaiah, R. Giese and J. A. Swenberg (1999). "A gas chromatography/electron capture/negative chemical ionization high-resolution mass spectrometry method for analysis of endogenous and exogenous N7-(2-hydroxyethyl)guanine in rodents and its potential for human biological monitoring." Chem Res Toxicol 12(8): 722-729.
Xu, W. L., A. R. Atti, M. Gatz, N. L. Pedersen, B. Johansson and L. Fratiglioni (2011). "Midlife overweight and obesity increase late-life dementia risk: a population-based twin study." Neurology 76(18): 1568-1574.
Yamada, K. and T. Nabeshima (2003). "Brain-derived neurotrophic factor/TrkB signaling in memory processes." J Pharmacol Sci 91(4): 267-270.
Yermilov, V., J. Rubio and H. Ohshima (1995). "Formation of 8-nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination." FEBS Lett 376(3): 207-210.
Zhang, F., Z. Kang, W. Li, Z. Xiao and X. Zhou (2012). "Roles of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signalling in Alzheimer''s disease." J Clin Neurosci 19(7): 946-949.
Zhu, W., W. Li and R. L. Silverstein (2012). "Advanced glycation end products induce a prothrombotic phenotype in mice via interaction with platelet CD36." Blood 119(25): 6136-6144.
Zipser, B. D., C. E. Johanson, L. Gonzalez, T. M. Berzin, R. Tavares, C. M. Hulette, M. P. Vitek, V. Hovanesian and E. G. Stopa (2007). "Microvascular injury and blood-brain barrier leakage in Alzheimer''s disease." Neurobiol Aging 28(7): 977-986.
Zlokovic, B. V. (2011). "Neurovascular pathways to neurodegeneration in Alzheimer''s disease and other disorders." Nat Rev Neurosci 12(12): 723-738.
Zorumski, C. F., S. Mennerick and Y. Izumi (2014). "Acute and chronic effects of ethanol on learning-related synaptic plasticity." Alcohol 48(1): 1-17.
Zuccato, C. and E. Cattaneo (2009). "Brain-derived neurotrophic factor in neurodegenerative diseases." Nat Rev Neurol 5(6): 311-322.
Zuendorf, G., N. Kerrouche, K. Herholz and J. C. Baron (2003). "Efficient principal component analysis for multivariate 3D voxel-based mapping of brain functional imaging data sets as applied to FDG-PET and normal aging." Hum Brain Mapp 18(1): 13-21.
Zunino, S. (2009). "Type 2 diabetes and glycemic response to grapes or grape products." J Nutr 139(9): 1794S-1800S.
陳達夫, 邱., 湯麗玉, 林忠蔚, 史宛玉, 陳榮基 (2016). 台灣長期照護機構失智患者之盛行率調查摘要.